<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Soni, Shivani</style></author><author><style face="normal" font="default" size="100%">Pandey, Ambarish</style></author><author><style face="normal" font="default" size="100%">Roy, Bhaskar</style></author><author><style face="normal" font="default" size="100%">Oh, Michael S.</style></author><author><style face="normal" font="default" size="100%">Chin, Kenneth T.</style></author><author><style face="normal" font="default" size="100%">Paraskar, Abhimanyu S.</style></author><author><style face="normal" font="default" size="100%">Sarangi, Sasmit</style></author><author><style face="normal" font="default" size="100%">Connor, Yamicia</style></author><author><style face="normal" font="default" size="100%">Sabbisetti, Venkata S.</style></author><author><style face="normal" font="default" size="100%">Kopparam, Jawahar</style></author><author><style face="normal" font="default" size="100%">Kulkarni, Ashish</style></author><author><style face="normal" font="default" size="100%">Muto, Katherine</style></author><author><style face="normal" font="default" size="100%">Amarasiriwardena, Chitra</style></author><author><style face="normal" font="default" size="100%">Jayawardene, Innocent</style></author><author><style face="normal" font="default" size="100%">Lupoli, Nicola</style></author><author><style face="normal" font="default" size="100%">Dinulescu, Daniela M.</style></author><author><style face="normal" font="default" size="100%">Bonventre, Joseph V.</style></author><author><style face="normal" font="default" size="100%">Mashelkar, Raghunath Anant</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity</style></title><secondary-title><style face="normal" font="default" size="100%">Proceedings of the National Academy of Sciences of the United States of America</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">chemotherapy</style></keyword><keyword><style  face="normal" font="default" size="100%">nanomedicine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUL</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">28</style></number><publisher><style face="normal" font="default" size="100%">NATL ACAD SCIENCES</style></publisher><pub-location><style face="normal" font="default" size="100%">2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA</style></pub-location><volume><style face="normal" font="default" size="100%">109</style></volume><pages><style face="normal" font="default" size="100%">11294-11299</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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 -&amp;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">28</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">10.66
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kulkarni, Ashish A.</style></author><author><style face="normal" font="default" size="100%">Roy, Bhaskar</style></author><author><style face="normal" font="default" size="100%">Rao, Poornima S.</style></author><author><style face="normal" font="default" size="100%">Wyant, Gregory A.</style></author><author><style face="normal" font="default" size="100%">Mahmoud, Ayaat</style></author><author><style face="normal" font="default" size="100%">Ramachandran, Madhumitha</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Goldman, Aaron</style></author><author><style face="normal" font="default" size="100%">Kotamraju, Venkata Ramana</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Mashelkar, Raghunath Anant</style></author><author><style face="normal" font="default" size="100%">Ruoslahti, Erkki</style></author><author><style face="normal" font="default" size="100%">Dinulescu, Daniela M.</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">23</style></number><publisher><style face="normal" font="default" size="100%">AMER ASSOC CANCER RESEARCH</style></publisher><pub-location><style face="normal" font="default" size="100%">615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA</style></pub-location><volume><style face="normal" font="default" size="100%">73</style></volume><pages><style face="normal" font="default" size="100%">6987-6997</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intratumoral concentration, and an insulin resistance ``class effect.'' This study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-alpha-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polythylen e glycol)]. The supramolecular nanoparticles (SNP) that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the SNPs exerted a temporally sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer treatment. (C)2013 AACR.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">23</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">9.284</style></custom4></record></records></xml>