Cooperative nanomaterial system to sensitize, target, and treat tumors.

TitleCooperative nanomaterial system to sensitize, target, and treat tumors.
Publication TypeJournal Article
Year of Publication2010
AuthorsPark J-H, von Maltzahn G, Xu MJue, Fogal V, Kotamraju VRamana, Ruoslahti E, Bhatia SN, Sailor MJ
JournalProc Natl Acad Sci U S A
Volume107
Issue3
Pagination981-6
Date Published2010 Jan 19
ISSN1091-6490
KeywordsAntineoplastic Agents, Cell Line, Tumor, Doxorubicin, Humans, Nanostructures, Neoplasms
Abstract

A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials. The first component is gold nanorod (NR) "activators" that populate the porous tumor vessels and act as photothermal antennas to specify tumor heating via remote near-infrared laser irradiation. We find that local tumor heating accelerates the recruitment of the second component: a targeted nanoparticle consisting of either magnetic nanoworms (NW) or doxorubicin-loaded liposomes (LP). The targeting species employed in this work is a cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) that binds to the stress-related protein, p32, which we find to be upregulated on the surface of tumor-associated cells upon thermal treatment. Mice containing xenografted MDA-MB-435 tumors that are treated with the combined NR/LyP-1LP therapeutic system display significant reductions in tumor volume compared with individual nanoparticles or untargeted cooperative system.

DOI10.1073/pnas.0909565107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20080556
PubMed Central IDPMC2824295
Grant List5-R01-CA124427 / CA / NCI NIH HHS / United States
U54 CA119335 / CA / NCI NIH HHS / United States
U54 CA119349 / CA / NCI NIH HHS / United States