02323nas a2200217   4500008004100000022001400041245015600055210006900211260000800280300001400288490000600302520153700308100002001845700001701865700001801882700002001900700001501920700002101935700001801956856013101974       2017                        eng d  a2470-134300aDrug-triggered self-assembly of linear polymer into nanoparticles for simultaneous delivery of hydrophobic and hydrophilic drugs in breast cancer cells0 aDrugtriggered selfassembly of linear polymer into nanoparticles   cDEC  a8730-87400 v23 a<p>Breast cancer is the most devastating disease among females globally. Conventional chemotherapeutic regimen relies on the use of highly cytotoxic drugs as monotherapy and combination therapy leading to severe side effects to the patients as collateral damage. Moreover, combining hydrophobic and hydrophilic drugs create erratic biodistribution and suboptimal medicinal outcome. Hence, packaging multiple drugs of diverse mechanisms of action and biodistribution for safe delivery into tumor tissues with optimal dosages is indispensable for next-generation breast cancer therapy. To address these, in this report, we describe a unique cisplatin-triggered self-assembly of linear polymer into 3D-spherical sub 200 nm particles. These nano-particles comprise a hydrophobic (paclitaxel) and hydrophilic drug (cisplatin) simultaneously in a single particle. Molecular dynamics simulation revealed hydrophilic-hydrophilic interaction and interchain H-bonding as underlying mechanisms of self-assembly. Confocal microscopy studies evidently demonstrated that these novel nanoparticles can home into lysosomes in breast cancer cells, fragment subcellular nuclei, and prevent cell division, leading to improved breast cancer cell death compared to free drug combination. Moreover, 3D-breast tumor spheroids were reduced remarkably by the treatment of these nanoparticles within 24 h. These dual-drug-loaded self-assembled polymeric nanoparticles have prospective to be translated into a clinical strategy for breast cancer patients.</p>1 aPalvai, Sandeep1 aAnandi, Libi1 aSarkar, Sujit1 aAugustus, Meera1 aRoy, Sudip1 aLahiri, Mayurika1 aBasu, Sudipta  uhttps://library.ncl.res.in/content/drug-triggered-self-assembly-linear-polymer-nanoparticles-simultaneous-delivery-hydrophobic02536nas a2200181   4500008004100000022001400041245010800055210006900163260000800232300001400240490000600254520188300260100002002143700002502163700002202188700001802210856012602228       2017                        eng d  a2470-134300aHyaluronic acid layered chimeric nanoparticles: targeting MAPK-P13K signaling hub in colon cancer cells0 aHyaluronic acid layered chimeric nanoparticles targeting MAPKP13  cNOV  a7868-78800 v23 a<p>Colon cancer has emerged as one of the most devastating diseases in the whole world. Mitogen-activated protein kinase (MAPK)-phosphatidylinsitol-3-kinase (PI3K) signaling hub has gained lots of attention due to its deregulation in colon cancer cells. However, selective targeting of oncogenic MAPK-PI3K hub in colon cancer has remained highly challenging, hence it has mostly been unexplored. To address this, we have engineered a hyaluronic acid layered lipid-based chimeric nanoparticle (HA-CNP) consisting of AZD6244 (MAPK inhibitor), PI103 (PI3K inhibitor), and cisplatin (DNA impairing drug) ratiometrically in a single particle. Electron microscopy (field emission scanning electron microscopy and atomic force microscopy) and dynamic light scattering were utilized to characterize the size, shape, morphology, and surface charge of the HA-CNPs. Fluorescent confocal laser scanning microscopy and flow cytometry analysis confirmed that HA-CNPs were taken up by HCT-116 colon cancer cells by merging of clathrin and CD44 receptor-mediated endocytosis along with macropinocytosis to home into acidic organelles (lysosomes) within 1 h. A gel electrophoresis study evidently established that HA-CNPs simultaneously inhibited MAPK-PI3K signaling hub with DNA damage in HCT-116 cells. These HA-CNPs stalled the cell cycle into G0/G1 phase, leading to induction of apoptosis (early and late) in colon cancer cells. Finally, these HA-CNPs exerted remarkable cytotoxicity in HCT-116 colon cancer cells at 24 h compared to that of the free triple drug cocktail as well as HA-coated dual drug-loaded nanoparticles without showing any cell death in healthy L929 fibroblast cells. These HA-coated CNPs have potential to be translated into clinics as a novel platform to perturb various oncogenic signaling hubs concomitantly toward next-generation targeted colon cancer therapy.</p>1 aPalvai, Sandeep1 aKuman, Meenu, Mahesh1 aSengupta, Poulonu1 aBasu, Sudipta  uhttps://library.ncl.res.in/content/hyaluronic-acid-layered-chimeric-nanoparticles-targeting-mapk-p13k-signaling-hub-colon