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

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.
AuthorsJi-Ho Park, Geoffrey von Maltzahn, Mary Jue Xu, Valentina Fogal, Venkata Ramana Kotamraju, Erkki Ruoslahti, Sangeeta N Bhatia, Michael J Sailor
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 3 Pg. 981-6 (Jan 19 2010) ISSN: 1091-6490 [Electronic] United States
PMID20080556 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Doxorubicin
Topics
  • Antineoplastic Agents (administration & dosage, therapeutic use)
  • Cell Line, Tumor
  • Doxorubicin (administration & dosage, therapeutic use)
  • Humans
  • Nanostructures
  • Neoplasms (drug therapy, therapy)

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