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Posted: April 15, 2008

Novel drug delivery methods: getting drugs to tumors quickly and with less toxicity

(Nanowerk News) As promising cancer therapies and drugs emerge, researchers strive to find ways to deliver them to patients with minimal side effects. At the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, researchers report that therapies delivered by “trojan horse” peptides and through the use of nanotechnology may enhance the effectiveness of cancer treatment.
Kousparou C, et al. Antennapedia ‘trojan’ peptide delivers p21 protein resulting in tumor eradication: Abstract 4908
Researchers report that using the Antennapedia protein as a “trojan horse” to pierce the outer layer of a cancer cell and deliver p21, a known tumor suppressor protein, successfully reduces malignant tumors in mice. Christina Kousparou, Ph.D., head of research at Trojantec Ltd, said intravenous treatment with p21 by this method brought the cancer cell growth and death cycle to a halt and slowed tumor growth. Mice given this protein also lived longer than a control group of animals, she reports.
Researchers had speculated that p21 would increase sensitivity to chemotherapy. The combination of p21 with chemotherapy resulted in total tumor eradication in 40 percent of animals and a reduction in tumor burden in 100 percent of animals, Kousparou reports.
“The efficacy of our anti-tumor growth modality in combination with conventionally used medication suggests that it can be considered as a promising therapeutic drug for the management of a wide range of carcinomas,” said Kousparou.
Siddiqui IA, et al. Nanochemoprevention: introducing a novel concept in cancer chemoprevention with a proof of principle for superior activity of green tea polyphenol epigallocatechin-3-gallate encapsulated in PLGA/PVA nanoparticles: Abstract 2102
Researchers may have found a way to effectively deliver green tea to a tumor, increasing its utility as a “chemopreventive” agent.
Although green tea has been shown in preclinical studies to have significant cancer prevention potential, its therapeutic use has been limited by lack of a method for delivering effective doses to cancer cells.
“Most biological processes, including those that are cancer-related, occur at the nanoscale, so we hypothesized that nanoparticle delivery of green tea polyphenol epigallocatechin-3 would be a possible method,” said Imtiaz A. Siddiqui, Ph.D., a research associate at the University of Wisconsin. Researchers encapsulated green tea polyphenol epigallocatechin-3-gallate in synthetic nanoparticles and evaluated the response in human prostate cancer cells.
An initial treatment with the nanoparticles alone without green tea showed negligible response, Siddiqui said. Adding tiny amounts of green tea to the nanoparticles, however, produced a significant response that persisted for 48 to 72 hours. Further experiments showed that treatment with nanoparticle-delivered green tea increased the rate of cancer cell death and decreased the number of new cell colonies.
“Validation of these cell culture data to animal model systems could pave the way for developing new avenues of cancer chemoprevention,” said Siddiqui.
Source: American Association for Cancer Research