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Edited by Mark E. Davis, California Institute of Technology, Pasadena, CA, and approved November 16, 2009 (received for review September 2, 2009)
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.
Footnotes
- 1To whom correspondence should be addressed: E-mail: msailor{at}ucsd.edu.
Author contributions: J.-H.P., G.v.M., E.R., S.N.B., and M.J.S. designed research; J.-H.P., G.v.M., M.J.X., V.F., E.R., S.N.B., and M.J.S. analyzed data; J.-H.P. and M.J.S. wrote the paper; J.-H.P., G.v.M., M.J.X., and V.F. performed research; and V.R.K. contributed new reagents/analytic tools.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0909565107/DCSupplemental.
Cooperative nanomaterial system to sensitize, target, and treat tumors
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