01987nas a2200253   4500008004100000022001400041245006000055210005900115260007100174300001400245490000600259520116700265653001701432653001601449653001801465653001501483653001701498100002601515700002401541700001801565700003201583700002501615856009301640       2009                        eng d  a1936-085100aFullerenol-cytotoxic conjugates for cancer chemotherapy0 aFullerenolcytotoxic conjugates for cancer chemotherapy  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcSEP  a2505-25140 v33 a<p>In the present study, we report the novel application of polyhydroxylated fullerenes (fullerenols) in cancer drug delivery. The facile synthetic procedure for generating multiple hydroxyl groups on the fullerene cage offers scope for high drug loading in addition to conferring hydrophilicity. Doxorubicin, a first line cancer chemotherapeutic, was conjugated to fullerenols through a carbamate linker, achieving ultrahigh loading efficiency. The drug-fullerenol conjugate was found to be relatively stable in phosphate buffer saline but temporally released the active drug when incubated with tumor cell lysate. The fullerenol-doxorubicin conjugate suppressed the proliferation of cancer cell-lines in vitro through a G2-M cell cycle block, resulting in apoptosis. Furthermore, in an in vivo murine tumor model, fullerenol-doxorubicin exhibited Comparable antitumor efficacy as free drug without the systemic toxicity of free doxorubicin. Additionally, we demonstrate that the fullerenol platform can be extended to other chemotherapeutic agents, such as the slightly water-soluble cisplatin, and can emerge as a new paradigm in the management of cancer.</p>10achemotherapy10adoxorubicin10adrug delivery10afullerenol10ananoparticle1 aChaudhuri, Padmaparna1 aParaskar, Abhimanyu1 aSoni, Shivani1 aMashelkar, Raghunath, Anant1 aSengupta, Shiladitya  uhttps://library.ncl.res.in/content/fullerenol-cytotoxic-conjugates-cancer-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-002541nas a2200313   4500008004100000022001400041245007700055210006900132260008000201300001600281490000800297520150100305653001701806653001801823653001501841653001701856653001301873100002101886700001801907700002001925700001901945700002801964700002001992700002102012700003302033700003202066700002502098856010402123       2016                        eng d  a0027-842400aReporter nanoparticle that monitors its anticancer efficacy in real time0 aReporter nanoparticle that monitors its anticancer efficacy in r  a2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAbNATL ACAD SCIENCEScAPR  aE2104-E21130 v1133 a<p>The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.</p>10achemotherapy10aimmunotherapy10amonitoring10ananoparticle10areporter1 aKulkarni, Ashish1 aRao, Poornima1 aNatarajan, Siva1 aGoldman, Aaron1 aSabbisetti, Venkata, S.1 aKhater, Yashika1 aKorimerla, Navya1 aChandrasekar, Vineethkrishna1 aMashelkar, Raghunath, Anant1 aSengupta, Shiladitya  uhttps://library.ncl.res.in/content/reporter-nanoparticle-monitors-its-anticancer-efficacy-real-time