Targeted nanoparticles that deliver a sustained, specific release of Paclitaxel to irradiated tumors.

Passarella RJ, Spratt DE, van der Ende AE, Phillips JG, Wu H, Sathiyakumar V, Zhou L, Hallahan DE, Harth E, Diaz R
Cancer Res. 2010 70 (11): 4550-9

PMID: 20484031 · PMCID: PMC2880200 · DOI:10.1158/0008-5472.CAN-10-0339

To capitalize on the response of tumor cells to XRT, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced cell surface receptor. Phage display biopanning identified Gly-Ile-Arg-Leu-Arg-Gly (GIRLRG) as a peptide that selectively recognizes tumors responding to XRT. Membrane protein extracts of irradiated glioma cells identified glucose-regulated protein GRP78 as the receptor target for GIRLRG. Antibodies to GRP78 blocked the binding of GIRLRG in vitro and in vivo. Conjugation of GIRLRG to a sustained-release nanoparticle drug delivery system yielded increased paclitaxel concentration and apoptosis in irradiated breast carcinomas for up to 3 weeks. Compared with controls, a single administration of the GIRLRG-targeted nanoparticle drug delivery system to irradiated tumors delayed the in vivo tumor tripling time by 55 days (P = 0.0001) in MDA-MB-231 and 12 days in GL261 (P < 0.005). This targeting agent combines a novel recombinant peptide with a paclitaxel-encapsulating nanoparticle that specifically targets irradiated tumors, increasing apoptosis and tumor growth delay in a manner superior to known chemotherapy approaches.

Copyright 2010 AACR.

MeSH Terms (22)

Animals Antineoplastic Agents, Phytogenic Apoptosis Bacteriophages Breast Neoplasms Cell Growth Processes Cell Line, Tumor Coculture Techniques Delayed-Action Preparations Drug Delivery Systems Endothelial Cells Glioma Heat-Shock Proteins Humans Mice Mice, Inbred C57BL Mice, Nude Nanoparticles Oligopeptides Paclitaxel Recombinant Proteins Xenograft Model Antitumor Assays

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