01870nas a2200229   4500008004100000022001400041245008800055210006900143260008000212300001400292490000800306520103400314653001101348653002401359100001801383700002101401700001801422700002401440700003201464700002501496856011901521       2009                        eng d  a0027-842400aNanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy0 aNanoparticlemediated targeting of MAPK signaling predisposes tum  a2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAbNATL ACAD SCIENCEScMAY  a7957-79610 v1063 a<p>The MAPK signal transduction cascade is dysregulated in a majority of human tumors. Here we report that a nanoparticle-mediated targeting of this pathway can optimize cancer chemotherapy. We engineered nanoparticles from a unique hexadentate-polyD, L-lactic acid-co-glycolic acid polymer chemically conjugated to PD98059, a selective MAPK inhibitor. The nanoparticles are taken up by cancer cells through endocytosis and demonstrate sustained release of the active agent, resulting in the inhibition of phosphorylation of downstream extracellular signal regulated kinase. We demonstrate that nanoparticle-mediated targeting of MAPK inhibits the proliferation of melanoma and lung carcinoma cells and induces apoptosis in vitro. Administration of the PD98059-nanoparticles in melanoma-bearing mice inhibits tumor growth and enhances the antitumor efficacy of cisplatin chemotherapy. Our study shows the nanoparticle-mediated delivery of signal transduction inhibitors can emerge as a unique paradigm in cancer chemotherapy.</p>10acancer10aSignal transduction1 aBasu, Sudipta1 aHarfouche, Rania1 aSoni, Shivani1 aChimote, Geetanjali1 aMashelkar, Raghunath, Anant1 aSengupta, Shiladitya  uhttps://library.ncl.res.in/content/nanoparticle-mediated-targeting-mapk-signaling-predisposes-tumor-chemotherapy-0