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-002140nas a2200361   4500008004100000022001400041245008800055210006900143260008000212300001600292490000800308520092900316653002701245653001101272653002101283653001701304653002401321100002601345700001801371700002101389700002501410700001901435700001901454700001701473700002401490700002401514700002301538700002201561700002201583700003201605700002501637856011601662       2010                        eng d  a0027-842400aCoupling growth-factor engineering with nanotechnology for therapeutic angiogenesis0 aCoupling growthfactor engineering with nanotechnology for therap  a2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAbNATL ACAD SCIENCEScAUG  a13608-136130 v1073 a<p>Therapeutic angiogenesis is an emerging paradigm for the management of ischemic pathologies. Proangiogenic Therapy is limited, however, by the current inability to deliver angiogenic factors in a sustained manner at the site of pathology. In this study, we investigated a unique nonglycosylated active fragment of hepatocyte growth factor/scatter factor, 1K1, which acts as a potent angiogenic agent in vitro and in a zebrafish embryo and a murine matrigel implant model. Furthermore, we demonstrate that nanoformulating 1K1 for sustained release temporally alters downstream signaling through the mitogen activated protein kinase pathway, and amplifies the angiogenic outcome. Merging protein engineering and nanotechnology offers exciting possibilities for the treatment of ischemic disease, and furthermore allows the selective targeting of downstream signaling pathways, which translates into discrete phenotypes.</p>10acardiovascular disease10aHGF/SF10aischemic disease10ananoparticle10aprotein engineering1 aRoy, Rituparna, Sinha1 aSoni, Shivani1 aHarfouche, Rania1 aVasudevan, Pooja, R.1 aHolmes, Oliver1 ade Jonge, Hugo1 aRowe, Arthur1 aParaskar, Abhimanyu1 aHentschel, Dirk, M.1 aChirgadze, Dimitri1 aBlundell, Tom, L.1 aGherardi, Ermanno1 aMashelkar, Raghunath, Anant1 aSengupta, Shiladitya  uhttps://library.ncl.res.in/content/coupling-growth-factor-engineering-nanotechnology-therapeutic-angiogenesis-0