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Technology Disclosure: 04-010 - 04-053, Cancer-Cell-Activated Instant-Intracellular-Drug-Releasing Nanoparticles for Chemotherapy 06-016 Degradable Nanogel for Drug Delivery

Cancer continues to be a major life-threatening disease. This disease is the second leading cause of death in the United States. In 2002, more than 1.2 million Americans were diagnosed with various cancers. Annual medical costs for cancer are in billions of dollars in the U.S.

Chemotherapy is one of the primary methods of treatment of cancer. It uses chemical agents to kill the cancer cells. Unfortunately, tumor cells respond only moderately to the current standard chemotherapy. The underlying reason for this insensitivity to the chemotherapy is that cancer cells have many defense mechanisms to resist the drug actions. They can reduce cell drug concentration by slowing the drug’s entry into the cells, ejecting drugs out of the cells with specialized pumps, and by converting drugs into harmless forms. Current therapeutic regiments, however, can only slowly deliver a low concentration of drugs to cancer cells in a discontinuous manner. As a result, the drug concentration in cancer cells is too low to effectively kill them. More importantly, the cancer cells surviving this low drug concentration are induced to become even more drug-insensitive, causing treatment failure.

Nanoparticles have been demonstrated to be able to preferentially deliver drugs to diseased tissues resulting in enhanced therapeutic efficacy, but to date those nanoparticles still have three major issues in treating cancer. First, they release a large portion of the drug immediately upon entering the bloodstream (i.e. burst release). This results in only a small portion of the drug reaching the cancer tissues, causing non-targeted drug release, low drug efficacy, toxicity to healthy tissues, and less medication available to fight the cancer. Second, they release only slowly after the initial “burst” release. This means that the drug cannot build up a concentration higher than the cells’ ability to purge itself of the drug, leading to ineffective killing of the cancer cells. The third issue is that the nanoparticles only slowly enter cancer cells, thus releasing drugs outside of the cancer cells rather than inside them.

To effectively overcome cancer drug resistance for high therapeutic efficacy, nanoparticles must have a fast cytoplasmic drug delivery to make drug influx into the cell surpass the capacity of all forms of drug resistance so that the drug builds up an effective cell-killing concentration. Such cytoplasmic drug delivery calls for fast cellular internalization of nanoparticles and fast drug release kinetics. Receptor-mediated endocytosis has been explored to enhance internalization by installing cell-specific ligand moieties on nanoparticle surfaces. However, the receptor-mediated endocytosis by itself is still not fast enough to deliver sufficient drug to the cells for efficient cell-killing. In addition, it is also limited by cell types and stages. There are also no applicable fast-drug releasing nanoparticles reported.

Researchers at the University of Wyoming have developed a patent-pending novel method of administering cancer treatment that will address the issues described above. Through the use of programmed nanoparticles combining three cell-uptake mechanisms (adsorption-mediated endocytosis, receptor-mediated endocytosis, and adsorption-enhanced receptor-mediated endocytosis) and a programmed fast-releasing mechanism, this method releases a faster delivery of cancer-fighting drugs into the cytoplasm of cancerous cells. The cell’s drug-resistance capacity is overwhelmed and a drug concentration is delivered well above the cells’ resistance threshold.

These nanoparticles can also be altered to inhibit premature drug release, enhance circulation time, and increase uptake of the drug by the cancer cells, thereby increasing the likelihood of effective treatment and termination of the cancer cells.

Our researchers have generated compelling data in a mouse model showing greatly enhanced chemotherapy results when the chemotherapy drug is bound to our nanoparticles. Please see the attached PowerPoint presentation. This research project was recently awarded $690,000 by American Cancer Society (read more).

If you would like to learn more about this novel method for cancer treatment and how your company may apply it in commercial situations, please contact the director of the University of Wyoming Research Products Center, Davona Douglass. We would be pleased to share further details.