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Nanoparticles Shown to Target Tumors, Avoid Adjacent Cells

Drug nanoparticle illustration

Drug nanoparticle illustration (National Cancer Institute)

22 March 2016. A small-scale clinical trial shows cancer drugs formulated into nanoparticles accumulate in solid tumors in humans, while avoiding adjacent healthy tissue. The team from California Institute of Technology in Pasadena published its findings yesterday (21 March) in the journal Proceedings of the National Academy of Sciences.

The CalTech team, led by chemical engineering professor Mark Davis, tested the drug camptothecin, a small-molecule or low molecular-weight compound normally administered through intravenous injection. In this study, camptothecin was bound to particles about 30 nanometers in size — 1 nanometer equals 1 billionth of a meter — using a technology developed by Cerulean Pharma, a company in Waltham, Massachusetts. Davis is an advisor and owns shares in Cerulean Pharma, which was also one of the study’s funders.

Nanoparticle drug delivery addresses a need for better targeting of powerful tumor-fighting drugs, while minimizing adverse side effects often experienced by recipients of conventional chemotherapy. The use of nanoparticles, can also make it possible to combine cancer drugs that would otherwise be too toxic, as well as deliver new classes of biologic therapies, such as short interfering RNAs.

“Right now,” says Davis in a CalTech statement, “if a doctor wants to use multiple drugs to treat a cancer, they often can’t do it because the cumulative toxic effects of the drugs would not be tolerated by the patient. With targeted nanoparticles, you have far fewer side effects, so it is anticipated that drug combination can be selected based on the biology and medicine rather than the limitations of the drugs.”

Earlier studies with lab animals shows cancer drugs delivered with nanoparticles improve the permeability and retention of their active compounds in tumors, but these effects up to now were not shown in humans. For this clinical trial, researchers recruited 9 patients at City of Hope cancer center in Duarte, California with gastric, gastroesophageal, or esophageal cancer, who were given the experimental drug developed by Cerulean Pharma code-named CRLX101 that delivers camptothecin bound to nanoparticles.

The team inspected tissue biopsies from the 9 patients’ tumors before, and 24 to 48 hours following the drug’s intravenous administration. The results show for all 9 of the participants, the drug-bound nanoparticles accumulated in the tumors — in 5 of the patients, the nanoparticles remained intact — while avoiding the adjacent healthy tissue. In 6 of the patients, tissue samples also show reductions in protein biomarkers associated with their tumors, carbonic anhydrase IX and topoisomerase I.

Because the trial was only a small-scale pilot study and did not use a similar non-treated group for comparison, the authors do not draw hard conclusions about nanoparticle cancer drug delivery from the results. But the findings do support conducting larger-scale studies designed to provide more solid evidence. Cerulean Pharma is sponsoring or collaborating in a number of these studies testing CRLX101 alone or with other drugs on ovarian, rectal, and other solid tumor cancers.

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