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One of the promises of using nanoparticles to deliver potent anticancer agents to tumors is that it is easy to coat nanoparticles with tumor-targeting molecules that should increase the amount of drug that reaches a tumor while decreasing the amount of drug that hits healthy tissue. Taking this idea one step further, researchers at Harvard Medical School and the Massachusetts Institute of Technology have developed a strategy for identifying what could be called tumor uptake molecules for use on nanoparticles. This new class of tumor-targeting agents boosts the amount of drug-loaded nanoparticles that get into cancer cells.
Omid Farokhzad and Robert Langer, both members of the MIT-Harvard Center for Cancer Nanotechnology Excellence (CCNE), led this study. The researchers published their findings in the journal ACS Nano.
The MIT-Harvard CCNE team focused their discovery efforts on molecules known as aptamers, which are small pieces of RNA or DNA that form three-dimensional shapes capable of binding tightly and specifically to designated targets. In most instances, aptamers are constructed to target a known biomolecule—a disease-associated protein, for example. In this case, the investigators took a different approach and instead targeted two biological properties—the ability to distinguish a prostate cancer cell from a normal prostate cell and the ability to get into the diseased cells. They performed this feat by starting with a huge pool of random RNA sequences and through an iterative process gradually enriched this pool for RNAs that targeted and entered prostate cancer cells. After 12 cycles of this enrichment process, the investigators identified a small number of aptamers that each displayed superior tumor targeting and uptake properties.
The researchers chose one of these aptamers and linked it to a polymer nanoparticle loaded with docetaxel, a potent anticancer agent. Experiments have so far shown that this construct has no effect on normal cells but is highly toxic to prostate cancer cells. The investigators are planning further studies in animal models of prostate cancer. They note that this approach is easily modified to finding targeting and uptake aptamers for any type of cancer cell.
About The National Cancer Institute (NCI)
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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