03013nas a2200409   4500008004100000022001400041245012700055210006900182260008000251300001600331490000800347520160500355653001701960653001701977100002201994700001802016700001802034700002102052700001702073700002002090700002202110700002802132700002002160700002002180700002802200700002202228700002102250700002002271700002902291700002602320700001902346700002702365700002602392700003202418700002502450856012802475       2012                        eng d  a0027-842400aCholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity0 aCholesteroltethered platinum IIbased supramolecular nanoparticle  a2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAbNATL ACAD SCIENCEScJUL  a11294-112990 v1093 a<p>Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O -&gt; Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC50 values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras(LSL/+/)Pten(fl/fl) ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a nextgeneration platinum-based agent in the clinics.</p>10achemotherapy10ananomedicine1 aSengupta, Poulomi1 aBasu, Sudipta1 aSoni, Shivani1 aPandey, Ambarish1 aRoy, Bhaskar1 aOh, Michael, S.1 aChin, Kenneth, T.1 aParaskar, Abhimanyu, S.1 aSarangi, Sasmit1 aConnor, Yamicia1 aSabbisetti, Venkata, S.1 aKopparam, Jawahar1 aKulkarni, Ashish1 aMuto, Katherine1 aAmarasiriwardena, Chitra1 aJayawardene, Innocent1 aLupoli, Nicola1 aDinulescu, Daniela, M.1 aBonventre, Joseph, V.1 aMashelkar, Raghunath, Anant1 aSengupta, Shiladitya  uhttps://library.ncl.res.in/content/cholesterol-tethered-platinum-ii-based-supramolecular-nanoparticle-increases-antitumor-0