65 replies to this topic

[Heliotrope]

If human trials are years away, then actual approval is probably years AND years away. Such is the pace of medical progress. My hope is that bio-informatics and computer simulation will speed up the process in the future. Of course this is an area where Imminst is on the forefront - sponsoring the F@H prize.

\]


even if human trial's avail. now, I wonder how many doctors would realize this or seriously encourage patients to do it. TFI's Dr. Kurt didn't even want to put him to some new chemo trials. I think it's also mentioned that Kurt is a partner @ a chemo outfit and is just making extra profit for himself

[Reno]

Targeted nanospheres find, penetrate, then fuel burning of melanoma

Any word on if or when any of these treatments are going through trials? As was mentioned in another thread, seems we have been reading about these wonderful nanotech cancer treatments for the last 5 to 10 years, yet none of them have broke through into regular treatments in a big way.

I just did a google news search. Here is an article talking about successful clinical trials of a nanoparticle bound with a breast cancer drug. It says it has a 50% response rate.

Click here -----> article

Here is another article.

Very cool Rexin-G nanoparticle video ----> Here

REXIN-G Shrinks Metastatic Tumors and Triples Survival Time in Chemotherapy-Resistant Pancreatic Cancer: Analysis of a U.S. Phase I/II Clinical Trial (Proceedings of ASCO GI Symposium 2009)


SAN MARINO, Calif., Jan. 20 /PRNewswire/ -- Epeius Biotechnologies (www.epeiusbiotech.com) announced the results of a U.S. Phase I/II study evaluating the safety and efficacy of Rexin-G in chemotherapy-resistant metastatic pancreatic cancer (ASCO GI Symposium, #249; Sant P Chawla, P.I., Santa Monica CA, January 2009). Rexin-G was well tolerated and there was no dose-limiting toxicity. At Dose Level I, three patients achieved stable disease with no tumor progression; and at Dose Level II, one patient had a 37% decrease in tumor size and five patients exhibited disease stabilization with no tumor progression. Importantly, Rexin-G improved patient survival in a dose-dependent manner: At Dose Level I, median progression-free survival was 3 months, and median over-all survival was 5 months, while at Dose Level II, median progression-free survival was greater than 3 months, and median over-all survival was greater than 9 months.

By direct comparison with a prior low-dose Phase I safety study (Galanis et al. 2008), the new "effective doses" of Rexin-G nearly tripled the overall survival time. Thus, this current Phase I/II study defines a critical pharmacological "threshold" for Rexin-G bioactivity in the treatment of metastatic pancreatic cancer. The present study confirms the overall safety of Rexin-G, and further demonstrates that Rexin-G monotherapy, at these defined dose levels, exhibits profound anti-tumor activity that prolongs both progression-free survival and over-all survival time in pancreatic cancer patients that had previously failed standard chemotherapy.

Rexin-G is the world's first and so far only targeted injectable genetic medicine that has been validated in the clinic (Nature Reviews/Genetics 2007). Injected intravenously, the targeted nanoparticles are designed to seek out and destroy both primary tumors and metastatic cancers that have spread throughout the body. The FDA has granted Orphan Drug Status for Rexin-G for the treatment of (i) pancreatic cancer, (ii) osteosarcoma, and (iii) soft tissue sarcoma, while the Philippine BFAD has granted accelerated approval of Rexin-G for the treatment of all solid tumors that are resistant to standard chemotherapy.

Epeius Biotechnologies Corporation is a privately held biopharmaceutical company dedicated to the advancement of genetic medicine with the development and commercialization of its tumor-targeted gene delivery systems. To learn more about ongoing clinical trials, please contact Dr. Erlinda M. Gordon at egordon@epeiusbiotech.com.

This release was issued on behalf of the above organization by Send2Press®, a unit of Neotrope®. http://www.Send2Press.com

source

Edited by bobscrachy, 03 February 2009 - 02:10 AM.

[davidd]

Very cool Rexin-G nanoparticle video ----> Here

That was great.

So is the next step another trial with dose III and IV? I mean, if this works as well as it appears in the video, then why did the patients die? Is it, like chemo, killing off the weakest cells and leaving some behind that are more immune and eventually kill the patients?

David

[Reno]

That was great.

So is the next step another trial with dose III and IV? I mean, if this works as well as it appears in the video, then why did the patients die? Is it, like chemo, killing off the weakest cells and leaving some behind that are more immune and eventually kill the patients?

David

I know that sometimes the tumors grow attached to important arteries. When they get killed by chemo the patient bleeds out. I also remember hearing that saturation has to be continuous for a while to make sure that all cells that are going to take up the new cancer agent get exposed. If the treatment is stopped to soon then some cancer cells survive to continue to spread.

Edited by bobscrachy, 03 February 2009 - 04:14 AM.

[Mind]

Another nanoparticle smart bomb for targetting cancer cells.

Another write-up about the research

This one using a plant virus as the delivery vehicle. Just wondering how well the virus will be able to get by the immune system? Will there be immunological side effects?

The researchers say that the virus is appealing in both its ability to survive outside of a plant host and its built-in "cargo space" of 17 nanometers, which can be used to carry chemotherapy drugs directly to tumor cells. The researchers deploy the virus by attaching small proteins, called signal peptides, to its exterior that cause the virus to "seek out" particular cells, such as cancer cells. Those same signal peptides serve as "passwords" that allow the virus to enter the cancer cell, where it releases its cargo.

"We had tried a number of different nanoparticles as cell-targeting vectors," Franzen says. "The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo."

Calcium is the key to keeping the virus' cargo enclosed. When the virus is in the bloodstream, calcium is also abundant. Inside individual cells, however, calcium levels are much lower, which allows the virus to open, delivering the cancer drugs only to the targeted cells.

"Another factor that makes the virus unique is the toughness of its shell," Lommel says. "When the virus is in a closed state, nothing will leak out of the interior, and when it does open,
it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug's efficacy."

[lucid]

Safer Nanoparticles Spotlight Tumors, Deliver Drugs
http://www.medicalne...cles/139918.php

Small is promising when it comes to illuminating tiny tumors or precisely delivering drugs, but many worry about the safety of nano-scale materials. Now a team of scientists has created miniscule flakes of silicon that glow brightly, last long enough to slowly release cancer drugs, then break down into harmless by-products.

"It is the first luminescent nanoparticle that was purposely designed to minimize toxic side effects," said Michael Sailor, a chemistry professor at the University of California, San Diego who led the study.

Many nanoparticles tested in research labs are too poisonous for use in humans.

"This new design meets a growing need for non-toxic alternatives that have a chance to make it into the clinic to treat human patients," Sailor said.

The particles inherently glow, a useful property that is most commonly achieved by including toxic organic chemicals or tiny structures called quantum dots, which can leave potentially harmful heavy metals in their wake.

When the researchers tested their safer nanoparticles in mice, they saw tumors glow for several hours, then dim as the particles broke down. Levels dropped noticeably in a week and were undetectable after four weeks, they report in Nature Materials February 22.

This is the first sudy to image tumors and organs using biodegradable silicon nanoparticles in live animals, the authors say.

The particles begin as thin wafers made porous with an electrical current then smashed to bits with ultrasound. Additional treatment alters the physical structure of the flakes to make them glow red when illuminated with ultraviolet light.

Luminescent particles can reveal tumors too tiny to detect by other means or allow a surgeon to be sure all of a cancerous growth has been removed.

These nanoparticles could also help deliver drugs safely, the researchers report. The cancer drug doxorubicin will stick to the pores and slowly escape as the silicon dissolves.

"The goal is to use the nanoparticles to chaperone the drug directly to the tumor, to release it into the tumor rather than other parts of the body," Sailor said.

Targeted delivery would allow doctors to use smaller doses of the drug. At doses high enough to be effective, when delivered to the whole body, doxorubicin often has toxic side effects.

At about 100 nanometers, these particles are bigger than many designed to deliver drugs, which can be just a few nanometers across - a thousand times smaller than the diameter of a human hair.

Their larger size contributes to both their effectiveness and their safety. Large particles can hold more of a drug. Yet they self-destruct, and the remnants can be filtered away by the kidneys.

Close examination of vulnerable organs like liver, spleen and kidney, which help to remove toxins, revealed no lasting changes in mice treated with the new nanoparticles.

----------------------------
Article adapted by Medical News Today from original press release.

[Mind]

Nanoparticles open door to cancer prevention

That's right, nanochemoprevention - trying to inhibit cancer growth and metastasis before it becomes a problem. I like the idea because "an ounce of prevention is worth a pound of cure".

This current research - not too much to right home about (yet) - is more of a proof of concept. The nano-modified ECGC was 10 times more bioactive and reduced PSA levels in animal models. Will it reduce reduce mortality rates?

One of the chief issues in chemoprevention—the use of biologically active molecules to thwart cancer before it gains a foothold in the body—is that any such agents must be exceedingly safe, since it is likely that a person at risk for cancer would need to take the chemopreventive agent on a regular basis for a long time. Because of this requirement, many investigators have been screening naturally occuring molecules for chemopreventive activity. One such molecule, the green tea component epigallocatechin-3-gallate (EGCG), has demonstrated chemopreventive potential in a wide range of in vitro and in vivo studies. However, the body rapidly degrades this compound, limiting its clinical utility.

The Wisconsin team solved this problem using nanoparticles. When the investigators loaded biocompatible polymer nanoparticles with EGCG, they boosted its cancer-preventing activity by more than tenfold. Additional experiments confirmed that this increase resulted from a significantly longer half-life for EGCG in the body. This longer half-life correlated with a reduction in serum prostate-specific antigen levels in animals with implanted human prostate tumors.

[Mind]

Light-activated molecular 'lock' controls blood clotting, drug delivery

I put this one here because the researchers involved mention a possible use in cancer treatment, but this is really a new nano-tool that could be used in many applications.

A lock-like molecule designed by University of Florida chemistry researchers clasps or unclasps based on exposure to light. In laboratory tests, the chemists put the lock on an enzyme involved in blood clotting. They then exposed the enzyme to visible and ultraviolet light. The clasp opened and closed, clotting the blood or letting it flow.
The results suggest that the biological hardware could one day be used to prevent the formation of tiny blood vessels that feed tumors. The little lock could also be placed in drugs, giving doctors the ability to release them only on diseased cells, tissues or organs -- maximizing their efficacy while preventing side effects from damage to healthy tissue.
Endoscopic lights inserted into the patient could unlock the drugs when desired -- or, the drugs could be activated by simply exposing the skin nearest the targets to near-infrared light, which penetrates the skin.

[Athanasios]

http://www.physorg.c...s165512266.html

excerpt:

Gold nanoshells are among the most promising new nanoscale therapeutics being developed to kill tumors, acting as antennas that turn light energy into heat that cooks cancer to death. Now, a multi-institutional research team has shown that polymer-coated gold nanorods one-up their spherical counterparts, with a single dose completely destroying all tumors in a nonhuman animal model of human cancer....

This looks very powerful as evidenced by how well it kills tumors, how there seems to be no or little recurrence, and how it is able to be used to gather important data. This is something that I believe will be able to move from efficacy in mice to efficacy in humans quite well.

[Mind]

This looks very powerful as evidenced by how well it kills tumors, how there seems to be no or little recurrence, and how it is able to be used to gather important data. This is something that I believe will be able to move from efficacy in mice to efficacy in humans quite well.

Seems every year we get better and better results in animal studies, yet almost nothing (in the nanotech/cancer realm) is making it into human treatment, although I agree that this particular treatment does seem more powerful.

One thing I am getting more concerned about is cost. See yet another story about "how much is life worth?" Nationalized health care systems are increasingly refusing treatment to expensive patients. Thankfully the U.S. system is still semi-private wherein potentially costly yet effective treatments are pursued.

[Athanasios]

What makes me very excited about the trend in cancer treatments is the simultaneous rapid advance in both treatment and diagnostics.

I tend to think that cost pressures on treatments will push us in the right direction. Think of the Da Vinci robot that 'costs' a lot of money to buy but, due to its effectiveness, ultimately cuts the cost of the procedure due to better outcome. Now think of how much resources can be saved as we move to better diagnostics and treatment of cancer. These 'game changing' technologies will still develop in a market with cost-pressures. Most of the R&D of both the Da Vinci and the gold nanoparticle treatment were done by government funding. If we drop out a lot of the more speculative drugs that are trying to get a small percent improvement over the competition's questionable drug, we might be better served.

Thanks for moving this to the pinned thread, I looked for it in bioscience and couldn't find it.

[Mind]

Microcapsules deliver chemo drugs directly to lung tumor.

It is still traditional chemo, but targeted chemo should lead to better outcomes. Also, nice to see that one of these therapies is in Phase II clinical trials. It is about time one of these "breakthrough nano-tech cancer treatments" is getting closer to actual clinical application.

While the concept behind their techniques is relatively the same, the materials used to make the bubbles differ. The Transave bubble is based on a lipid and the Strathclyde University team has developed a bubble made of a surfactant, cholesterol and dicetylphosphate.

Katharine Carter, a member of the Strathclyde University research team, said the reagents that make up their bubble are more robust, and the manufacturing method has the potential to be much simpler.

Neither technique is commercially available; however, Transave has already taken its drug-delivery system to stage two clinical trials, while Strathclyde is still performing animal testing.

Carter said her team is not worried about its system being beaten to market. ‘It’s better to go in second because you can see things that you can maybe do better,’ she added.

The technique would work by placing drug-containing bubbles in the solution container of a nebuliser. Carter said their animal trials indicate a patient would only have to breathe in the bubbles for 6.5 minutes.

When the bubbles reach the lung, she added, they will be met by a vast amount of macrophages, which are white blood cells that break down pathogens with special enzymes.

Carter explained that these macrophages would recognise the bubbles as a pathogen and bust them open. ‘The drug will then be released locally at the cells and into the environment nearby,’ she said.

[Vgamer1]

I hope you guys don't mind me stealing all these links for the Internetworking Team, because I already did. These are all great! Thanks for all the research!

[Vgamer1]

I actually have some articles to add from the INW articles list:

http://www.lef.org/m...ife-Span_01.htm

http://www.dailymail...ased-cells.html

http://blogs.discove...of-lung-cancer/

[garlicknots]

Hey,

Sorry if this has been posted already--I searched and didn't find it. Promising. Very promising. I hope that stage 3 trials begin soon and I hope that they open them to more than recurrent gbms.

http://www.nanowerk....ewsid=13339.php

http://www.magforce....ls/glioblastom1

Fairly despondent that I'm getting radiation these days to appease my parents with so much on the horizon.

[Reno]

Nanotechnology team discover how to capture tumor cells in bloodstream

A team led by University of Arkansas for Medical Sciences (UAMS) researchers on the cutting edge of nanotechnology has found a way to capture tumor cells in the bloodstream that could dramatically improve earlier cancer diagnosis and prevent deadly metastasis.
The discovery was published Nov. 15 in Nature Nanotechnology, a prestigious monthly print and online journal that provides a forum for leading research papers in all areas of nanoscience and nanotechnology ("In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells").
Vladimir Zharov, director of the Phillips Classic Laser and Nanomedicine Laboratory at UAMS, said his team of researchers can inject a cocktail of magnetic and gold nanoparticles with a special biological coating into the bloodstream to target circulating tumor cells. A magnet attached to the skin above peripheral blood vessels can then capture the cells.
“By magnetically collecting most of the tumor cells from blood circulating in vessels throughout the whole body, this new method can potentially increase specificity and sensitivity up to 1,000 times compared to existing technology,” Zharov said.
Once the tumor cells are targeted and captured by the magnet, they can either be microsurgically removed from vessels for further genetic analysis or can be noninvasively eradicated directly in blood vessels by laser irradiation through the skin that is still safe for normal blood cells.
Zharov’s team, which has recently been awarded more than $3.7 million in clinical nanomedicine-related grants, includes Ekaterina Galanzha, M.D., Ph.D., an assistant professor in the UAMS Department of Otolaryngology; Evgeny Shashkov, Ph.D., a visiting scholar and laser physicist; Thomas Kelly, Ph.D., associate professor in the UAMS Department of Pathology; Jin-Woo Kim, Ph.D., a nano-biotechnologist at the University of Arkansas at Fayetteville; and Lily Yang, Ph.D., a biologist from Emory University.
A second related discovery by Zharov’s team was published in Cancer Research in October ("In vivo, Noninvasive, Label-Free Detection and Eradication of Circulating Metastatic Melanoma Cells Using Two-Color Photoacoustic Flow Cytometry with a Diode Laser"). It demonstrated that periodic laser irradiation of blood vessels decreases the level of circulating metastatic tumor cells more than 10 times and eventually led to an interruption of metastasis development in distant organs.
“Further study could determine whether these new cancer treatments are effective enough to be used alone or if they should be used in conjunction with conventional cancer therapy,” Zharov said.
The discovery highlighted in Cancer Research earned Zharov and his team a selection for Faculty of 1000 Biology, an award-winning Web site that highlights and evaluates the most interesting papers published in the biological sciences. Papers are selected based on the recommendations of more than 2000 of the world’s top researchers.
The new discoveries can also be applied for early detection of cancer recurrence and for real-time monitoring therapy efficiency involving the counting of circulating tumor cells.
“Most cancer deaths are the result of metastasis due to the spread of tumor cells from the primary tumor through the blood,” said James Suen, M.D., chairman of the UAMS Winthrop P. Rockefeller Cancer Institute’s Department of Otolaryngology, Head and Neck Surgery. “This revolutionary discovery introduced by Zharov’s team gives many patients hope in earlier cancer diagnosis and better treatment. The nanomedicine-based approach to read and treat whole blood in the body with nanotechnology seems to be universal, with further development holding the promise for the diagnosis and treatment of many diseases, including infections or cardiovascular disorders to prevent stroke and heart attack.”

source

[Mind]

Nanoparticles that deliver 2 or more drugs simultaneously could defeat pancreatic cancer.

As you probably could have guessed, this is another mouse success story to be tested in humans in "just a few years". Nice to see so many nanotech approaches being tested, but it would be nice to see some human results as well.

Shiladitya Sengupta, an assistant professor of medicine and health sciences and technology at Harvard Medical School, calls the results of Hasan's mouse experiments "dramatic." He says, "In the context of pancreatic cancer, [the results are] outstanding, because there's no therapy."

Sengupta did not participate in Hasan's research, but he originated the idea of drug delivery using nanocells. Technology Review recognized him for this idea with a 2005 TR35 award. He cofounded Cerulean Pharma to commercialize the nanocell platform and other nanopharmaceutical delivery methods. But one tricky aspect of the technology is that it must be individually optimized for every new combination of drugs, he notes.

Hasan's team has already developed a second nanocell designed to prevent pancreatic cancers from developing resistance to chemotherapy, a very common problem. Other researchers have identified two proteins, EGFR and MET, as particularly important in the development and growth of pancreatic cancer. In fact, in cancer cell lines in the lab, when biologists block EGFR, the cells increase their production of MET, and vice versa. So to better control the tumors, Hasan's team set out to target EGFR and MET simultaneously, while again hitting the tumor with light to increase the effectiveness of the treatment.

This second nanocell required a more sophisticated design. Rai started with a small molecule called PHA-66572, which inhibits the MET protein, and confined it in the same sort of solid polymer nanoparticle used in the first nanocell. He then surrounded those nanoparticles with cetuximab, an antibody that blocks EGFR. Finally, he incorporated Visudyne into a lipid sphere that he used to encapsulate these two layers.

Zheng says that tumors shrank dramatically in mice that had been implanted with pancreatic cancers and then given a single injection of the nanocells followed by light therapy. He is still measuring the effects on metastasis, but since the MET protein is active in most cancers that have metastasized (not just pancreatic cancer), the researchers are optimistic that the growth-factor nanocells will significantly decrease the number and size of metastases as well.

[revenant]

This is cought my eye: http://www.physorg.c...s181837761.html

[Reno]

RNA interference delivered using nanoparticles hits target in human patients

A multi-institutional team of researchers and clinicians has published the first proof that a targeted nanoparticle can traffic into tumors, deliver double-stranded small interfering RNAs (siRNAs), and turn off the production of an important cancer protein using a mechanism known as RNA interference (RNAi). Moreover, the team provided the first demonstration that this new type of therapy, infused into the bloodstream, can make its way to human tumors in a dose-dependent fashion, that is, a higher number of nanoparticles sent into the body leads to a higher number of nanoparticles in the tumor cells. These two findings were achieved in phase I clinical trials in which the investigators are testing a nanoparticle-siRNA construct as an anticancer therapy.
These results, which were published in the journal Nature ("Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles"), demonstrate the feasibility of using both nanoparticles and RNAi-based therapeutics in patients, and open the door for future "game-changing" therapeutics that attack cancer and other diseases at the genetic level, says team leader Mark E. Davis of the California Institute of Technology. Dr. Davis is also a member of the Nanosystems Biology Cancer Center, a National Cancer Institute Center for Cancer Nanotechnology Excellence.
The discovery of RNAi, the mechanism by which double strands of RNA silence genes, won researchers Andrew Fire and Craig Mello the 2006 Nobel Prize in Physiology or Medicine. The scientists first reported finding this novel mechanism in worms in a 1998 Nature paper. Since then, the potential for this type of gene inhibition to lead to new therapies for diseases such as cancer has been highly touted.
"RNAi is a new way to stop the production of proteins," says Dr. Davis. What makes it such a potentially powerful tool, he adds, is the fact that its target is not a protein, the typical target for anticancer drugs. The vulnerable areas of a protein may be hidden within its three-dimensional folds, making it difficult for many therapeutics to reach them. In contrast, RNA interference targets the messenger RNA (mRNA) that encodes the information needed to make a protein in the first place.
"In principle," says Dr. Davis, "that means every protein now is druggable because its inhibition is accomplished by destroying the mRNA. And we can go after mRNAs in a very designed way given all the genomic data that are and will become available."
Still, there have been numerous potential roadblocks to the application of RNAi technology as therapy in humans. One of the most problematic has been finding a way to ferry the therapeutics, which are made up of fragile siRNAs, into tumor cells after direct injection into the bloodstream. Dr. Davis, however, had a solution. Even before the discovery of RNAi, he and his team had begun working on ways to deliver nucleic acids to cells via the blood stream. They eventually created a four-component system, featuring a unique polymer called cyclodextrin, that self-assembles in the presence of RNA into a targeted, siRNA-containing nanoparticle. The siRNA delivery system is under clinical development by Calando Pharmaceuticals, Inc., based in Pasadena, California.
"These nanoparticles are able to take the siRNAs to the targeted site within the body," says Dr. Davis. Once they reach their target, in this case, the cancer cells within tumors, the nanoparticles enter the cells and release the siRNAs.
As part of their study, the team was able to detect and image nanoparticles inside cells biopsied from the tumors of several of the phase I trial's participants. In addition, Dr. Davis and his colleagues were able to show that the higher the nanoparticle dose administered to the patient, the higher the number of particles found inside the tumor cells—the first example of this kind of dose-dependent response using targeted nanoparticles. Even better, Dr. Davis says, the evidence showed the siRNAs had done their job. In the tumor cells analyzed by the researchers, the mRNA encoding the cell-growth protein ribonucleotide reductase – the target of the siRNA encapsulated in the nanoparticle – had been degraded. This degradation, in turn, led to a loss of the protein.
More to the point, the mRNA fragments found were exactly the length and sequence they should be if they'd been cleaved in the spot targeted by the siRNA, notes Dr. Davis. "It's the first time anyone has found an RNA fragment from a patient's cells showing the mRNA was cut at exactly the right base via the RNAi mechanism," he says. "It proves that the RNAi mechanism can happen using siRNA in a human."

source

[Reno]

Nanofibers carry toxic peptides into cancer cells

Researchers have long known that certain peptides are capable of killing cells by inserting themselves into the cell membranes and disrupting normal membrane structure and function. Now, researchers at Northwestern University have learned how to deliver these cytotoxic peptides to tumor cells using self-assembling nanofibers that can slip into cancer cells and allow the toxic peptides to do their job from inside the cell. The research team, led by Samuel Stupp and Vincent Cryns, published its work in the journal Cancer Research ("Induction of Cancer Cell Death by Self-assembling Nanostructures Incorporating a Cytotoxic Peptide"). Dr. Stupp is a member of the Nanomaterials Cancer Diagnostic and Therapeutic Center, a National Cancer Institute Center for Cancer Nanotechnology Excellence.
To create their nanofibers, the researchers first synthesized molecules called peptide amphiphiles. These molecules fold into sheet-like structures that have one water-seeking, or hydrophilic, side and one water-avoiding, or hydrophobic side. When mixed in solution, this peptide self-assembles into long, nanometer-thin fibers. When the cytotoxic peptide was attached to one end of the peptide amphiphiles, it ended up decorating the surface of the fiber.
When added to breast cancer cells, this construct easily entered the cells, while the cytotoxic peptide alone did not. The nanostrucutres also induced breast cancer cell death, while the cytotoxic peptide alone did not. One surprising finding was that the nanostructures triggered cell death more effectively in breast tumor cells than they did when added to normal breast cells, suggesting that the fibers themselves may have some selectivity for tumor cells.

source

[Reno]

Radioactive gold nanoparticles destroy prostate tumors, leaving healthy tissue untouched

One of the promises of nanoparticles as delivery agents for cancer therapeutics is that they will attack tumors while sparing healthy tissue from the damage normally associated with today's anticancer therapies. That promise is closer to realization thanks to the results of a study in which tumor-bearing mice were treated with a single dose of radioactive gold nanoparticles.
The results of this study, which was led by Kattesh Katti and Raghuraman Kannan, both of the University of Missouri at Colombia, were published in the journal Nanomedicine ("Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-198AuNP nanoconstruct in prostate tumor–bearing mice"). Dr. Katti is the principle investigator of the Hybrid Nanoparticles in Imaging and Therapy of Prostate Cancer project, a National Cancer Institute Cancer Nanotechnology Platform Partnership.
For this study, Dr. Katti's research group prepared their gold nanoparticles using the radioactive isotope gold-198. They then coated the resulting nanoparticles with gum Arabic glycoprotein to create biocompatible nanoparticles capable of escaping the blood stream and accumulating in tumors. Studies in mice showed that these nanoparticles, when injected into the blood stream, only accumulate in implanted human prostate tumors, with minimal or no leakage of radioactivity into other organs.
Tumor-bearing animals injected with a single dose of the nanoparticles were followed for three weeks. At the end of that time, tumor volume in the treated animals was 82% smaller compared to tumors in animals that received non-radioactive nanoparticles coated with gum Arabic glycoprotein. In addition, the treated animals did not lose weight during the three-week period, while the untreated animals experienced significant weight loss. The researchers also examined various blood cells for signs of radiation damage and found none, an encouraging sign that these nanoparticles are only toxic to tumors.

source

[Reno]

Nano-bio-chip checks for oral cancer

The gentle touch of a brush on the tongue or cheek can help detect oral cancer with success rates comparable to more invasive techniques like biopsies, according to preliminary studies by researchers at Rice University, the University of Texas Health Science Centers at Houston and San Antonio and the University of Texas M.D. Anderson Cancer Center. A new test that uses Rice's diagnostic nano-bio-chip was found to be 97 percent "sensitive" and 93 percent specific in detecting which patients had malignant or premalignant lesions, results that compared well with traditional tests.
The results of this study, which was led by John McDevitt, were published in the journal Cancer Prevention Research ("Nano-Bio-Chip Sensor Platform for Examination of Oral Exfoliative Cytology"). Oral cancer afflicts more than 300,000 people a year, including 35,000 in the United States alone. The five-year survival rate is 60 percent, but if oral cancer is detected early, that rate rises to 90 percent.
"One of the key discoveries in this paper is to show that the miniaturized, noninvasive approach produces about the same result as the pathologists do," said Dr. McDevitt, whose group developed the novel nano-bio-chip technology.
Dr. McDevitt and his team are working to create an inexpensive chip that can differentiate premalignant lesions from the 95 percent of lesions that will not become cancerous. The minimally invasive technique would deliver results in 15 minutes instead of several days, as lab-based diagnostics do now. Instead of an invasive, painful biopsy, the new procedure requires just a light brush of the lesion on the cheek or tongue with an instrument that looks like a toothbrush.
"This area of diagnostics and testing has been terribly challenging for the scientific and clinical community," said McDevitt, who came to Rice from the University of Texas at Austin in 2009. "Part of the problem is that there are no good tools currently available that work in a reliable way."
He said patients with suspicious lesions, which are usually discovered by dentists or oral surgeons, end up getting scalpel or punch biopsies as often as every six months. "People trained in this area don't have any trouble finding lesions," McDevitt said. "The issue is the next step — taking a chunk of someone's cheek. The heart of this paper is developing a more humane and less painful way to do that diagnosis, and our technique has shown remarkable success in early trials."
Nano-bio-chips are small, semiconductor-based devices that combine the ability to capture, stain and analyze biomarkers for a variety of diseases. Researchers hope the eventual deployment of nano-bio-chips will dramatically cut the cost of medical diagnostics and contribute significantly to the task of bringing quality health care to the world.
The new study compared results of traditional diagnostic tests with those obtained with nano-bio-chips on a small sample of 52 participants. All of the patients had visible oral lesions of leukoplakia or erythroplakia and had been referred to specialists for surgical biopsies or removal of the lesions.
The chips should also be able to see when an abnormality turns precancerous. "You want to catch it early on, as it's transforming from pre-cancer to the earliest stages of cancer, and get it in stage one. Then the five-year survival rate is very high," he said. "Currently, most of the time, it's captured in stage three, when the survivability is very low." The device is on the verge of entering a more extensive trial that will involve 500 patients in Houston, San Antonio and England.

source

[Reno]

Nanoporous particles deliver novel molecular therapies to tumors

Using nanoporous silicon particles, two teams of investigators have created drug delivery vehicles capable of ferrying labile molecular therapies deep into the body. Both groups believe their new drug delivery vehicles create new opportunities for developing innovative anticancer therapies.
Mauro Ferrari, of the University of Texas Health Sciences Center at Houston, led a research team aiming to develop new methods of delivering therapeutic small interfering RNA (siRNA) molecules to tumors. He and his colleagues published their results of their studies in the journal Cancer Research ("Sustained Small Interfering RNA Delivery by Mesoporous Silicon Particles"). Karl Erik Hellstrom, of the University of Washington, and Jun Liu and Chenghong Lei, both of the Pacific Northwest National Laboratory (PNNL), led the research group developing methods for delivering therapeutic antibodies to tumors. Their research was published in the Journal of the American Chemical Society ("Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy"). Dr. Ferrari is the principal investigator of one of the National Cancer Institute’s (NCI) Physical Sciences in Oncology Centers, and he played a seminal role in establishing the NCI’s Alliance for Nanotechnology in Cancer.
siRNA is promising approach to anticancer therapy, and one anticancer siRNA molecule is now in clinical trials in humans (click here for a recent story). However, siRNA molecules are rapidly degraded in the body, so delivering them to tumors requires help.
Dr. Ferrari’s team approached this problem by first encapsulating siRNA molecules in lipid-based nanoparticles. Earlier work by his team had already demonstrated that these lipid nanoparticles could deliver siRNA molecules to tumors, but achieving a therapeutic effect in tumor-bearing mice required twice-weekly injections for many weeks. To reduce the number of injections needed, Dr. Ferrari and his colleagues decided to load their nanoparticle-siRNA construct into the pores of biocompatible nanoporous silicon particles.They then injected their drug delivery vehicle into mice with human ovarian tumors.
When the researchers examined the mice three weeks later, the researchers found that tumors had shrunken markedly and that the siRNA agent was still exerting its biological effect. The investigators also found that toxicities were minimal or non-existent.
Meanwhile, the University of Washington-PNNL team used nanoporous silicon to entrap large numbers of monoclonal antibodies that target a specific tumor-associated protein known as CTLA-4. Monoclonal antibodies targeting CTLA-4 have been shown to produce marked antitumor effects in human clinical trials, but therapeutic levels of this antibody can trigger unwanted autoimmune reactions and other severe side effects. Drs. Hellstrom, Liu, and Lei and their collaborators reasoned that nanoporous silicon particles could act as a reservoir that would maintain therapeutic levels of antibody right at the tumor site while reducing the overall amount of antibody circulating freely in the body.
To test their hypothesis, the investigators injected their construct directly into melanomas growing in mice. As a control, a second set of mice received CTLA-4 monoclonal antibodies injected into the peritoneal cavity. Results of this experiment showed that CTLA-4 monoclonal antibodies delivered using nanoporous silicon produced a month-long suppression of tumor growth with no toxicity, while CTLA-4 antibodies alone had little effect on tumor growth. The first group of animals also lived far longer than the second group.

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[1kgcoffee]

I'm currently invested in one of these cancer nanotech research companies - arrowhead research. This looks like it could be the next big thing.

[Reno]

Drug delivery system hits tumors but spares kidneys

Harvard and Brigham and Women's Hospital researchers have devised a method that may allow clinicians to use higher doses of a powerful chemotherapy drug that has been limited because it is toxic not only to tumors but to patients' kidneys.
Using nanotechnology to improve a cancer treatment: Drug delivery system hits tumors but spares kidneys
Cambridge, MA | Posted on June 26th, 2010

The research, conducted in laboratory animals, marries chemistry and nanotechnology to deliver toxic platinum atoms to tumors while almost entirely blocking the platinum from accumulating in the kidney, according to Shiladitya Sengupta, a Harvard assistant professor of medicine and health sciences and technology whose Laboratory for Nanomedicine at Harvard-affiliated Brigham and Women's Hospital conducted the work.

Sengupta has focused his research for three years on cisplatin, a powerful anti-cancer drug used in first-line chemotherapy. Sengupta said the drug, discovered about 40 years ago, has many positive aspects. It is relatively inexpensive and effective against many cancers. Its toxicity, however, limits its use.

"Even if you can see amazing results as an anti-tumor therapy, you can't give more," Sengupta said.

Despite several attempts, cisplatin hasn't been improved upon, Sengupta said. Two similar drugs that also incorporate platinum are on the market, but while they are less toxic to the kidney, they are also less active against tumors.

Though the chemistry involved is complex, the key to cisplatin's effectiveness — and its toxicity — lies in how easily it releases platinum, both at the tumor site and, undesirably, in the kidneys.

Manufacturers of the two alternative drugs have reduced those drugs' toxicity by making them hold onto their platinum more tightly. Sengupta's work took a different track, however. Understanding that particles greater than five nanometers in size would not be absorbed by the kidney, he set out to engineer a super-sized cisplatin.

Understanding the chemical properties of the cisplatin molecule and the laws that govern molecular folding, his team designed a polymer that would bind to cisplatin, much as a thread runs through a bead's central hole. By stringing together enough cisplatin, the whole molecule wrapped itself into a ball, 100 nanometers in size, too large to enter the kidney.

It took a couple of tries to get the molecular design right, Sengupta said. Though the initial design proved nontoxic to kidneys, it wasn't as effective as the original cisplatin. Sengupta and colleagues tweaked the chemical formula so the molecule didn't hold quite so tightly to the platinum atoms.

Studies conducted by Basar Bilgicer, assistant professor at the University of Notre Dame, showed that the molecule accumulated in tumor tissue, whose leaky blood vessels allowed it to pass out of the capillaries that feed the tumor. The molecule is too large to pass into other tissues, such as the kidney, lungs, liver, and spleen. Once lodged in the tumor, the higher acidity there caused the molecule to fall apart, dumping its toxic load on the cancerous tissue.

"It showed absolutely minimal toxicity to the kidney," Sengupta said.

The new compound has been found to be effective against lung and breast cancers. Instructor in pathology Daniela Dinulescu at Brigham and Women's Hospital also demonstrated that the nano-compound outperformed cisplatin in a transgenic ovarian cancer model that mimics the disease in humans.

The research, which received funding from the National Institutes of Health and the Defense Department's Breast Cancer Research Program, has not been tried in humans, and would require potentially lengthy testing before being ready for patient care.

Described in this week's Proceedings of the National Academy of Sciences, the project also included researchers at the University of Notre Dame, the Harvard-MIT Division of Health Sciences and Technology, the Dana-Farber Cancer Institute, the National Chemical Laboratory in Pune, India, and the Translational Health Science and Technology Institute in New Delhi.

Sengupta praised the work and creativity of fellows Abhimanyu Paraskar and Shivani Soni on the project.

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[Reno]

Super-sizing a cancer drug minimizes side effects

One of the first chemotherapy drugs given to patients diagnosed with cancer — especially lung, ovarian or breast cancer — is cisplatin, a platinum-containing compound that gums up tumor cells' DNA. Cisplatin does a good job of killing those tumor cells, but it can also seriously damage the kidneys, which receive high doses of cisplatin because they filter the blood.

Now a team of scientists at the Harvard-MIT Division of Health Sciences and Technology (HST) has come up with a new way to package cisplatin into nanoparticles that are too big to enter the kidneys. The new compound could spare patients the usual side effects and allow doctors to administer higher doses of the drug, says Shiladitya Sengupta, leader of the research team.


Crystals of cisplatin, a platinum compound that is used as a chemotherapy drug, are shown here
Crystals of cisplatin, a platinum compound that is used as a chemotherapy drug, are shown here. (Image: National Cancer Institute)

"We could give so much more cisplatin than is now possible," says Sengupta, an assistant professor of HST. "You could wipe out the tumor by carpet-bombing it."

Tumors in mice treated with the new cisplatin nanoparticle shrank to half the size of those treated with traditional cisplatin, with minimal side effects. The findings were reported in the Proceedings of the National Academy of Sciences in June.

Beads on a string

Doctors began using cisplatin to treat cancer in the 1970s. Early on, doctors recognized that it harmed the kidneys, and cancer researchers began looking for alternatives. In the past few decades, the FDA has approved two less-toxic derivatives of cisplatin: carboplatin and oxaliplatin. However, those drugs don't kill tumor cells as successfully as cisplatin.

Cisplatin's effectiveness lies in how easily it releases its platinum molecule, freeing it to cross-link DNA strands, disrupting cell division and forcing the cell to undergo suicide. Carboplatin and oxaliplatin are less effective (but less toxic) than cisplatin because they hold on to their platinum atoms more tightly.

Sengupta and his colleagues took a new approach to making cisplatin safer: stringing cisplatin molecules together into a nanoparticle that is too large to get into the kidneys. (It has been shown that the kidneys cannot absorb particles larger than five nanometers — about 1/10,000th the diameter of a human hair).

His team designed a polymer that binds to cisplatin, arranging the molecules like beads on a string. The string then winds itself into a nanoparticle about 100 nanometers long — much too large to fit into the kidneys. However, the particles can still reach tumor cells because tumors are surrounded by "leaky" blood vessels, which have 500-nanometer pores.

Their first nanoparticle proved less effective than cisplatin, so they tweaked the polymer to make it hold a little less tightly to platinum, and ended up with a molecule with a tumor-killing power similar to cisplatin's. However, because its side effects are minimal, the nanoparticle can be delivered in higher doses.

Daniela Dinulescu, an author of the paper and pathology instructor at Brigham and Women's Hospital in Boston, showed that the nanoparticles outperformed cisplatin in mice engineered to develop ovarian cancer. The researchers also showed it to be effective against lung and breast tumor cells grown in the lab. Once the tumor cells die, the immune system clears platinum from the body.

The research was funded by the Department of Defense Breast Cancer Research Program and the National Institutes of Health.
It is difficult to develop and gain approval for new platinum-based compounds, says Nicholas Farrell, professor of inorganic chemistry at Virginia Commonwealth University, but he believes Sengupta's new nanoparticles are promising. "If successful, the approach promises to maintain the status of cisplatin as one of the most useful drugs available to the clinician," says Farrell.

The MIT researchers are now working on new variants of the nanoparticles that would be easier to manufacture. They are also making plans to test the nanoparticles in clinical trials, which Sengupta hopes will get underway within the next two years. The polymer used for the nanoparticle backbone is similar to malic acid, a natural product of cellular metabolism, so Sengupta is optimistic that it will prove safe in humans.

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[Reno]

The side effects of chemotherapy could be largely wiped out.

The side effects of chemotherapy could be largely wiped out by a so-called "magic bullet" nanotechnology system being researched in Dubai, according to an associate professor at Dubai Pharmacy College.
Dr Aliasgar Shahiwala is looking into using nano-particles that would release chemotherapy drugs only on contact with cancerous cells. The amount of treatment needed to eliminate tumours could be reduced by 95 per cent should the research prove successful, he said.

"When you take normal medicine it diffuses throughout the body," said Dr Shahiwala. "It doesn't differentiate between the normal cell and the diseased cell. Using nanotechnology, you are specifically targeting the drugs to the diseased organs. Because all of the drug is targeted in this way, you also require a smaller dose. That is why nano-particles are called 'magic bullets'."

There is likely to be plenty of demand should the treatment be approved. Cancer cases are rising by as much as five per cent a year on a global basis, said Dr Falah al Khatib, a consultant clinic oncologist at the Gulf International Cancer Centre in Abu Dhabi.

The market for oncology drugs will be worth US$80 billion (Dh294bn) in global sales by 2012, according to the research house IMS.

However, the UK-based technology adviser PA Consulting has warned that large pharmaceutical companies have been slow to catch on to nanomedicines, a market expected to be worth a staggering US$220bn by 2015.

"Companies are starting to focus their efforts in this direction," Dr Shahiwala said. "Instead of finding new drugs they are directing their research in how they can use better their existing drugs."

Typical cancer treatment side effects such as hair loss, nausea and vomiting would be almost completely eliminated by the new technology, Dr Shahiwala said.

"Chemotherapy is a very traumatic experience," he said. "By using nanotechnology-based treatments, these side effects will be reduced by 90 per cent at least."

The research is being conducted in tandem with facilities around the world, which are also investigating the possibility that chemotherapy drugs can be delivered in a similar manner. Nano-particles, typically slightly larger than atoms, are being used in medicine as part of wider research in which nanotechnology is being applied to fields as diverse as nutrition and building materials.

Dr Shahiwala said his research has not yet reached a stage where it had attracted research from drugmakers. However, he is working on several areas, such as water solubility of oil-based drugs, which would iron out some of the potential problems with treatments currently on the market.

Experts believe the technology should come into its own in the near future and have the potential to revolutionise the field. "This is an emerging area of ongoing research," said Dr Thomas Faunce, an associate professor of law and medicine at Australia National University who has researched nanotechnology's public health ramifications. "These delivery systems are still being researched around the world but they contain massive potential for the treatment of cancer."
The technology's practical applications began in 2008, when the US processed foods manufacturer Kraft conceived of a "programmable drink" comprised of millions of nano-carriers in a colourless, tasteless liquid. Depending on which particles were stimulated, the drink could then be converted into cola or orange juice.

Dr Saeed Ahmed Khan, the dean of Dubai Pharmacy College, said it was likely that nanotechnology-based drugs would one day be widely available. "They are less costly and more effective," he said.

That would be welcome news to Ingrid Valles Po, a breast cancer survivor in Dubai. She said it could be a breakthrough that would make treatment easier should it come to fruition. "I know how hard it was for me when I did chemo and was always tired and down," she said. "If this will reduce those feelings and keep up our strength while fighting this battle, it will definitely be something I will opt for and recommend."

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Edited by Reno, 08 November 2010 - 05:30 AM.

[Reno]

I would rather see an alternative to chemo, but seeing it perfected as a targeted treatment is a fantastic leap forward.

Invention could improve cancer drug delivery, lessen harmful effects of chemotherapy

University of Arizona researchers may have found a way to deliver chemotherapeutic drugs to cancer tissues in controlled doses without harming healthy body cells.

If successful, the invention of gold-coated liposomes could make chemotherapy more effective to destroy cancer cells and alleviate the harmful side effects that can result from the treatment.

The invention by Marek Romanowski, an associate professor in the department of biomedical engineering in the College of Engineering at the UA, and his lab team doesn't have a silver lining. Better: It has a lining of gold. The secret to non-invasively controlling the release of chemotherapeutic drugs lies in nano-scale capsules made of lipids and coated with a fine layer of gold.

Chemotherapeutic drugs are sometimes encased in small capsules called liposomes, which are made of organic lipids that are already present in human cells. The lipid encasing keeps the body's immune system from attacking the foreign molecule before it can deliver the drug.

Once released into the bloodstream, drug-carrying liposomes accumulate around a cancer tumor because of a property known as leaky vasculature: Tumor cells have extra openings to blood vessels to take in nutrients carried in the bloodstream, usually because they are trying to grow more quickly than normal cells. The extra blood flow means that more nutrients, and also more liposomes, are likely to accumulate in the tumor cells where they eventually break down and release the drug into the cells, leading to cell death.

The highly toxic drugs used for chemotherapy destroy cancer cells, but with no way to discriminate between cell types, they can also damage healthy cells. This damage to the body's normal, healthy cells leads to the side effects normally associated with chemotherapy treatments: anemia, hair loss, vomiting – as cells that make up stomach lining are destroyed – and nausea, among others.

Keys in a lock

To better target cancer cells, the UA team attached liposomes to signal molecules called ligands, which interact with specific cell receptors like keys in a lock.

"It all depends on the disease that we're targeting, but in the case of tumor cells, they over-express certain receptors for several reasons. One is tumor cells are proliferating very quickly, and so they're over-expressing a lot of nutrient receptors because they want to divide faster," said Xenia Kachur, a third-year graduate student in the Biomedical Engineering Graduate Interdisciplinary Program, or GIDP. The extra receptors make the liposomes more likely to latch onto and get inside tumor cells than normal cells.

As they degrade, liposomes release drugs bit-by-bit in an uncontrolled fashion, which may not effectively destroy tumor cells. Said Sarah Leung, a fourth-year graduate student in the biomedical engineering GIDP who also is in the Romanowski lab: "There's a particular concentration at which you have optimal results, so below that you don't have enough of the drug to get a good response, and above that it might be even more toxic."

The new invention could allow doctors to control the amount of drug released at a time, and to release the drug only in the tumor region, thereby protecting healthy cells from damage caused by the drug. This is where the gold lining comes in.

Drugs coated in gold

"A property of gold is that it can convert near infrared light into heat," said Kachur. "By putting gold on the surface of these liposomes, we can then put in a stimulus such as near-infrared light. The gold converts the light into heat, the heat causes the liposome to become leaky, and then whatever's really concentrated inside can diffuse out through the leaky liposome."

"Infrared light penetrates the deepest through the body because it interacts the least with most tissues, and it also prevents a lot of the heating that your body might [otherwise] experience," said Kachur.

The theory goes that the amount of infrared light can be varied to control the amount of drug that is released from the gold-coated liposomes.

"By using more or less light, you can release more or less of the drug and time the responses as well, so when you trigger light, some drug will leak, you can trigger it again and have more drug leak, or you can wait a little while, let the drug disperse, do its thing, then trigger it again. It allows for a lot more freedom with the release process," said Leung. "By having this very triggered response you can hit that therapeutic window."

Despite increased blood-flow to tumor cells and the key-in-lock action of the ligands, some liposomes may still end up inside healthy cells. In that case, the gold-coating could potentially act to prevent release of the toxic drug to the healthy cells.

By selectively shining the infrared light only in the tumor region, doctors could make sure only liposomes in the tumor region are able to release the drug.

"Once you know where the tumors are, you can go ahead and point your light source toward those areas. Whatever else is left will leave the body or may be slowly released, but not to as high or as toxic of levels as it would be if you just injected the drug systemically," said Leung.

The invention has another bonus: "The gold-coated liposome is biodegradable, which is one of the best parts of our system," said Leung. Currently there are no approved chemotherapeutic treatments that allow the gold nanostructures to be eliminated from the body by the body's own mechanisms, said Leung.

Kidneys, the organs that normally filter waste molecules out of the blood, have a limit as to the size of molecule they can filter. "Because of the size it degrades into, our system should be clearable via the kidney, which is really unique," said Leung.

There still are many steps to take to test the invention before it could be used in cancer therapy. But if successful, gold-coated liposomes could provide a method to target chemotherapeutic drugs to cancer cells, non-invasively trigger the drugs' release using infrared light and provide a way for the body naturally to filter the drug from the bloodstream.
One day, cancer patients could potentially receive chemotherapy treatments with confidence that the drugs will effectively destroy cancer cells, and without fear of suffering any harmful side effects.

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[Reno]

Nanoparticles Deliver One-Two Therapeutic Punch to Kill Tumor Cells

The standard approach to cancer therapy today is to mix and match chemotherapy drugs in order to attack tumors in multiple ways. Now, two separate teams of investigators have demonstrated that using nanoparticles to deliver multiple drugs simultaneously can produce a synergistic effect that boosts the cell-killing ability of both drugs.

In one study, a team of investigators at Northwestern University has shown that they can combine two powerful but extremely toxic anticancer agents - cisplatin and doxorubicin - in one polymer nanoparticle, producing a substantial boost in their ability of the combination to destroy tumors. In addition, the two-in-one nanoparticle reduces the amount of both drugs needed to kill cancer cells, which presumably would reduce the toxic side effects associated with these drugs.

SonBinh Nguyen and Thomas O'Halloran led this study, which was published in the Journal of the American Chemical Society. Dr. O'Halloran is the co-principal investigator of one of 12 Cancer Nanotechnology Platform Partnerships funded by the National Cancer Institute Alliance for Nanotechnology in Cancer. He is also a member of the Northwestern University Center for Cancer Nanotechnology Excellence (CCNE), which is also part of the Alliance for Nanotechnology in Cancer.

Though originally designed to carry arsenic trioxide to solid tumors, the nanoparticles used in this study are proving to be quite versatile in their ability to ferry a wide range of cargos to malignancies. In this study, the investigators wanted to see if delivering two drugs in one nanoparticle offered any advantages of delivering them without the nanoparticle or in separate nanoparticles. The nanoparticles, which the researchers call nanobins, are made by encasing a liposome inside a pH-responsive polymer cage. In this case, doxorubicin is entrapped within the liposome's core, while cisplatin was entrapped in the polymer cage.

In an initial set of experiments, the investigators determined that a 5 to 1 ratio of cisplatin to doxorubicin was the most effective at treating ovarian tumors when the two drugs were combined in the same nanoparticle. When the two drugs were administered at this ratio but with each in its own nanoparticle, the combination was not only less effective at killing malignant cells, but the two drugs appeared to be interfering with each other, a phenomenon often observed in clinical practice. Administering the two drugs in the same nanoparticle ensures that the drugs are hitting their intracellular targets at the same time, which is what likely leads to the synergism observed in this study.

Meanwhile, Mansoor Amiji and Zhenfeng Duan, co-principle investigators of the Cancer Nanotechnology Platform Partnership at Northeastern University, have shown that a different type of polymer nanoparticle can also deliver two anticancer agents simultaneously and as a result can kill cancer cells that have become resistant to drug therapy. In this case, the researchers synthesized biocompatible polymer nanoparticles that entrapped paclitaxel and lonidamine and that targeted the epidermal growth factor receptor (EGFR) that is overexpressed on highly aggressive tumors. When added to tumor cells growing in culture, the nanoparticle containing both drugs was far more effective at killing the drug-resistance cells than when the two drugs were co-administered in separate nanoparticles. The investigators reported their findings in the journal Molecular Pharmaceutics.

In a separate set of experiments, the results of which were published in the journal Angewandte Chemie International Edition, Drs. Nguyen and O'Halloran, joined by Thomas Meade, another member of the Northwestern CCNE, demonstrated that nanobins can also co-deliver a therapeutic and magnetic resonance imaging agent to tumors. In this study, the researchers loaded the anticancer agent gemcitabine into the nanobin's core and added a gadolinium magnetic resonance contrast agent to the nanobin's surface. When added to mouse tumor cells, the nanobins were taken up rapidly and the nanobins were clearly visible in magnetic resonance images. In addition, the nanoparticles released their gemcitabine payload once the nanobins were taken up by the cultured cells.

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