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

Ralph J. Passarella, Daniel E. Spratt, Alice E. Van Der Ende, John G. Phillips, Hongmei Wu, Vasanth Sathiyakumar, Li Zhou, Dennis E. Hallahan, Eva Harth, Roberto Diaz

Research output: Contribution to journalArticlepeer-review

131 Scopus citations


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.

Original languageEnglish
Pages (from-to)4550-4559
Number of pages10
JournalCancer research
Issue number11
StatePublished - Jun 1 2010


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