Fully synthetic virus-like nanoparticles targeting prostate cancer cells

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	BIOCHEM/CHEM-5

* FARE Award Winner

Authors

• Y Chen
• SG Tarasov
• V Gaponenko
• OMZ Zack Howard
• JJ Oppenheim
• M Dyba
• S Subramanian
• NI Tarasova

Abstract

Significant efforts have been devoted to the development of nanoparticular delivering systems targeting tumors, since these systems are expected to lower toxicity, increase anti-cancer effectiveness, improve bioavailability of drugs and reduce the cost of treatments. Useful lessons in specific cell and organ delivery can be learned from nature. Viral particles are able to deliver whole proteins and large nucleic acid molecules to certain types of cells. We have found that properly derivatized synthetic analogs of transmembrane domains of membrane proteins can self-assemble into virus-like particles in aqueous solutions. A 24-amino acid peptide corresponding to the second transmembrane helix of the CXCR4 chemokine receptor adopts a predominantly beta-type conformation in aqueous solution and self-assembles into uniform round nanoparticles. The particles spontaneously fuse with the cell membrane and inhibit CXCR4 function in vitro and hamper CXCR4-dependent tumor metastasis in vivo. Anchoring of the nanoparticles to the cell membrane through gastrin-releasing peptide receptor(GRPR), luteinizing hormone-releasing hormone (LHRH) receptor and specific membrane antigen (PSMA), overexpressed on prostate tumor cells, facilitates fusion similar to that of a viral particle. The approach is likely to generate a new type of therapeutic agents for the effective treatment of advanced prostate cancer.

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