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.