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

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 -> 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.

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-003180nas a2200301 4500008004100000022001400041245013900055210006900194260009800263300001400361490000700375520203500382100002502417700001702442700002202459700002302481700001902504700002902523700002202552700001902574700003102593700001802624700003202642700002102674700002702695700002502722856013102747 2013 eng d a0008-547200aSupramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy0 aSupramolecular nanoparticles that target phosphoinositide3kinase a615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USAbAMER ASSOC CANCER RESEARCHcDEC a6987-69970 v733 a

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.

1 aKulkarni, Ashish, A.1 aRoy, Bhaskar1 aRao, Poornima, S.1 aWyant, Gregory, A.1 aMahmoud, Ayaat1 aRamachandran, Madhumitha1 aSengupta, Poulomi1 aGoldman, Aaron1 aKotamraju, Venkata, Ramana1 aBasu, Sudipta1 aMashelkar, Raghunath, Anant1 aRuoslahti, Erkki1 aDinulescu, Daniela, M.1 aSengupta, Shiladitya uhttps://library.ncl.res.in/content/supramolecular-nanoparticles-target-phosphoinositide-3-kinase-overcome-insulin-resistance-001789nas a2200205 4500008004100000245014600041210006900187260000800256300001400264490000600278520103400284100002401318700001601342700001701358700002201375700001901397700002501416700001801441856012401459 2016 eng d00aEngineering and in vitro evaluation of acid labile cholesterol tethered MG132 nanoparticle fortargeting ubiquitin-proteasome system in cancer0 aEngineering and in vitro evaluation of acid labile cholesterol t cOCT a5099-51060 v13 aIn recent years, proteasome has evolved as one of the important alternative targets in cancer chemotherapy. However, selective targeting of proteasome system in cancer cells still remains a major challenge. To address this, a potent peptide based proteasome inhibitor MG132 was chemically conjugated with biocompatible-biodegradable cholesterol by acid cleavable hydrazone linkage. Spherical nanoparticles (MG132-NPs) were engineered from cholesterol-MG132 conjugate. Increased amount of free MG132 was released from these nanoparticles in acidic environment compared to physiological milieu in a slow and controlled manner. These MG132-NPs were taken up by breast cancer MCF7 cells into lysosomes within 6 h. Proteasome system was inhibited by these MG132-NPs leading to stabilization of beta-catenin, cyclin A and cyclin B in HEK-293T cells. Interestingly, MG132-NPs induced much improved cell death in drug resistant MDA-MB-231 cells with insignificant toxicity in healthy cells (HEK293 and L929) even in higher concentration.1 aGhosh, Chandramouli1 aGupta, Neha1 aMore, Piyush1 aSengupta, Poulomi1 aMallick, Abhik1 aSantra, Manas, Kumar1 aBasu, Sudipta uhttps://library.ncl.res.in/content/engineering-and-vitro-evaluation-acid-labile-cholesterol-tethered-mg132-nanoparticle01296nas a2200193 4500008004100000245012000041210006900161260000800230300001400238490000700252520059900259100001700858700001900875700001700894700002200911700002100933700001800954856013000972 2017 eng d00aCisplatin-induced self-assembly of graphene oxide sheets into spherical nanoparticles for damaging sub-cellular DNA0 aCisplatininduced selfassembly of graphene oxide sheets into sphe cJAN a1409-14120 v533 aThis report describes the hitherto unobserved cisplatin induced self-assembly of 2D-graphene oxide sheets into 3D-spherical nano-scale particles. These nanoparticles can encompass dual DNA damaging drugs simultaneously. A combination of confocal microscopy, gel electrophoresis and flow cytometry studies clearly demonstrated that these novel nanoparticles can internalize into cancer cells by endocytosis, localize into lysosomes, and damage DNA, leading to apoptosis. Cell viability assays indicated that these nanoparticles were more cytotoxic towards cancer cells compared to healthy cells.1 aNandi, Aditi1 aMallick, Abhik1 aMore, Piyush1 aSengupta, Poulomi1 aBallav, Nirmalya1 aBasu, Sudipta uhttps://library.ncl.res.in/content/cisplatin-induced-self-assembly-graphene-oxide-sheets-spherical-nanoparticles-damaging-sub01006nas a2200109 4500008004100000245004200041210004200083300000700125520066800132100002200800856007400822 2017 eng d00aRecent innovations in coronary stents0 aRecent innovations in coronary stents a123 aIn heart diseases, there are frequent incidents of narrowing or blocking coronary arteries by fatty plaque deposition. As a result, blood pressure rises and the arteries weaken. This can lead to rapid rupture of the blood vessels, also known as heart attack or brain stroke. In some cases the arteries lose elasticity over old age. Heart stent or coronary stent inserts in the blocked/fragile region of coronary artery. It helps to expand the artery to allow free flow of blood and consequently, reduces blood pressure. Over past 20 years there are many modifications and innovations in the field of cardiac stents, in this chapter we will discuss few of those. 1 aSengupta, Poulomi uhttps://library.ncl.res.in/content/recent-innovations-coronary-stents02089nas a2200289 4500008004100000022001400041245011400055210006900169260000900238300001200247490000800259520111300267653001401380653001801394653002001412653003401432653004901466653001301515653001701528100001801545700001901563700002201582700001701604700002201621700002501643856013101668 2018 eng d a0144-861700aElectrospinning of non-ionic cellulose ethers/polyvinyl alcohol nanofibers: characterization and applications0 aElectrospinning of nonionic cellulose etherspolyvinyl alcohol na cFEB  a175-1820 v1813 a

The morphology of spin-coated films and electrospun fibers of ethyl hydroxy ethyl cellulose (EHEC), hydrophobically modified ethyl hydroxy ethyl cellulose (HM-EHEC) and their blends with Poly(vinyl alcohol) (PVA) was examined by AFM, SEM and contact angle measurements. These polysaccharides upon blending with PVA exhibited smooth surface which was evidenced by Atomic Force Microscopy (AFM) observation. The electrospinnability of above polysaccharides with PVA was demonstrated for the first time. The oriented fibers could be obtained using a rotating disc collector. Contact angles of spin-coated films and electrospun fibers were discussed in terms of hydrophobicity and wetting characteristics. Further, The nanofibers of EHEC/PVA were in-situ crosslinked using citric acid and were used for controlled release of an antibacterial drug, Chlorhexidine Digluconate (ChD). In-vitro studies of cytotoxicity, cell growth and cell proliferation were performed using L929 mouse fibroblast cells. These nanofiber mats show potential in drug delivery and as scaffolds in tissue engineering applications.

10acellulose10adrug delivery10aelectrospinning10aEthyl hydroxy ethyl cellulose10aHydrophobically modified ethyl hydroxy ethyl10ascaffold10aSpin coating1 aWali, Ashwini1 aZhang, Yucheng1 aSengupta, Poulomi1 aHigaki, Yuji1 aTakahara, Atsushi1 aBadiger, Manohar, V. uhttps://library.ncl.res.in/content/electrospinning-non-ionic-cellulose-etherspolyvinyl-alcohol-nanofibers-characterization-and02210nas a2200277 4500008004100000022001300041245014900054210006900203260000900272300001600281490000600297520121800303653003101521653003401552653001801586653003701604653001301641653001301654653002201667653002201689653001501711653002301726100002201749700003101771856013001802 2018 eng d a2470134300aSurface modification of polymers for tissue engineering applications: arginine acts as a sticky protein equivalent for viable cell accommodation0 aSurface modification of polymers for tissue engineering applicat cAPR  a4242–42510 v33 a

Hydrophobic polymers, for their favorable mechanical properties, are a popular choice as permanent bioimplants. These materials remain absolutely bioinert for years, but throw up challenges when it comes to fast integration with healthy tissue. Addressing this, herein, we present a surface-modification technique of converting the hydrophobic surface of a polymeric film into a hydrophilic one using a layer-by-layer assembly process involving gold nanoparticles and small molecules like amino acids. These films showed much improved animal cell (murine fibroblast) adherence properties compared to commercially available tissue culture plates. Moreover, arginine-modified films exhibited a nearly equivalent cell viability compared to the films modified with the natural extracellular matrix component fibronectin. The surface hydrophilicity and roughness of our novel film were characterized by contact angle measurement and atomic force microscopy. Cell counting, fluorescence microscopy, cell viability, and collagen estimation assay were employed to demonstrate that our film favored a much improved cell adherence, and accommodation in comparison to the commercially available tissue culture plates.

10aCell and Molecular biology10aExtracellular matrix proteins10aNanoparticles10aPhysical and chemical properties10aPolymers10aProteins10aSurface structure10aSurface treatment10aThin films10atissue engineering1 aSengupta, Poulomi1 aPrasad, Bhagavatula, L. V. uhttps://library.ncl.res.in/content/surface-modification-polymers-tissue-engineering-applications-arginine-acts-sticky-protein01862nas a2200169 4500008004100000022001400041245009400055210006900149260000800218300001600226490000600242520125300248100002201501700001901523700003001542856012001572 2020 eng d a2470-134300aDevelopment of a smart scaffold for sequential cancer chemotherapy and tissue engineering0 aDevelopment of a smart scaffold for sequential cancer chemothera cAUG a20724-207330 v53 a

The fabrication of a dual-functional drug-containing porous polymeric scaffold by layer-by-layer surface modification involving citrate-stabilized gold nanoparticles and cisplatin molecules is being reported. These scaffolds were characterized by electron microscopy and X-ray photoelectron spectroscopy. The capability of the scaffolds to release hydrated cisplatin in a slow and sustained manner over two days is established. Most importantly, the scaffolds turn nontoxic and cell-friendly after drug release, thus allowing the noncancerous fibroblast cells to adhere and proliferate (from 5000 cells to 16,000 cells in 6 days), becoming a potential solution toward an effective drug-carrying scaffold for volume-filling applications. The scaffold-mediated cancer cell killing and fibroblast cell proliferation were confirmed by fluorescence microscopy imaging, flow cytometry, and cell proliferation assays. We surmise that such a dual-purpose (drug-delivery and volume-filler) scaffold could help avoid the multiple surgical interventions needed for tumor surgery and cosmetic corrections. To the best of our knowledge, this is the first example of scaffolds with such a dual functionality which gets manifested in a sequential manner.

1 aSengupta, Poulomi1 aAgrawal, Vinay1 aPrasad, Bhagavatula L. V. uhttps://library.ncl.res.in/content/development-smart-scaffold-sequential-cancer-chemotherapy-and-tissue-engineering02207nas a2200241 4500008004100000022001400041245009600055210006900151260000800220300001100228490000800239520135800247653002801605653002901633653003201662653004701694100001701741700001701758700002101775700002201796700002101818856012601839 2021 eng d a1751-616100aMechanical and microstructural studies in a polysaccharide-acrylate double network hydrogel0 aMechanical and microstructural studies in a polysaccharideacryla cDEC a1048390 v1243 aPolymeric hydrogels continue to find a wide range of applications. However, a major drawback of hydrogels is the lack of mechanical strength. In this regard, ``Double Network Hydrogels'' (DN) have shown great promise recently. The toughness in DN hydrogels originates from the synergistic effect of two polymeric networks. In this work, we have synthesized a DN hydrogel consisting of a tightly cross linked carboxymethylcellulose (CMC) as the first network and loosely cross linked poly(hydroxyethylacrylate) (PHEA) as a second network (CMC-PHEADN). The required flexibility in the second network (PHEA) was induced by the presence of a small amount of stearyl methacrylate (SM) as a co-monomer in hydroxyl ethyl acrylate (HEA). The compressive strength of the CMC-PEHA-DN hydrogel was found to be 280 times more than that of CMC-SN hydrogel, and the presence of SM in DN hydrogels showed better recovery after deformation. Cell viability studies showed the biocompatibility of DN hydrogels. The micro-structural analysis of DN xerogels by 3D X-ray Microtomography indicated the presence of oriented pores in size range of 30-40 mu m. To the best of our knowledge, Microtomography was used for the first time to study the DN gels. These hydrogels can be used to develop implants that can withstand prolonged stress and expand the life span of implants.10aCarboxymethyl cellulose10aDouble network hydrogels10aPoly(hydroxyethyl acrylate)10aPoly(hydroxyethyl-co-stearyl methacrylate)1 aTorris, Arun1 aNair, Sanoop1 aMol, K., P. Raji1 aSengupta, Poulomi1 aBadiger, Manohar uhttps://library.ncl.res.in/content/mechanical-and-microstructural-studies-polysaccharide-acrylate-double-network-hydrogel02992nas a2200349 4500008004100000022001400041245010700055210006900162260000900231300001100240490000700251520191400258653000902172653001402181653001602195653001502211653001302226100001502239700001402254700002202268700002402290700002002314700001902334700002202353700001802375700002202393700002302415700002502438700002602463700002202489856013102511 2021 eng d a2234-943X00aUnbiased phenotype-based screen identifies therapeutic agents selective for metastatic prostate cancer0 aUnbiased phenotypebased screen identifies therapeutic agents sel cMAR  a5941410 v103 a

In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients' prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.

10abone10acarcinoma10adrug-screen10aMetastasis10aProstate1 aChung, Ivy1 aZhou, Kun1 aBarrows, Courtney1 aBanyard, Jacqueline1 aWilson, Arianne1 aRummel, Nathan1 aMizokami, Atsushi1 aBasu, Sudipta1 aSengupta, Poulomi1 aShaikh, Badaruddin1 aSengupta, Shiladitya1 aBielenberg, Diane, R.1 aZetter, Bruce, R. uhttps://library.ncl.res.in/content/unbiased-phenotype-based-screen-identifies-therapeutic-agents-selective-metastatic-prostate02257nas a2200265 4500008004100000245015100041210006900192260000800261300000900269490000700278520133600285653001901621653002401640653001901664653001701683653001901700100001601719700002201735700002101757700002201778700002201800700001901822700001801841856013201859 2022 eng d00aImproved mucoadhesion, permeation and in vitro anticancer potential of synthesized thiolated acacia and karaya gum combination: a systematic study0 aImproved mucoadhesion permeation and in vitro anticancer potenti cOCT a68290 v273 a

Thiolation of polymers is one of the most appropriate approaches to impart higher mechanical strength and mucoadhesion. Thiol modification of gum karaya and gum acacia was carried out by esterification with 80% thioglycolic acid. FTIR, DSC and XRD confirmed the completion of thiolation reaction. Anticancer potential of developed thiomer was studied on cervical cancer cell lines (HeLa) and more than 60% of human cervical cell lines (HeLa) were inhibited at concentration of 5 mu g/100 mu L. Immobilized thiol groups were found to be 0.8511 mmol/g as determined by Ellman's method. Cytotoxicity studies on L929 fibroblast cell lines indicated thiomers were biocompatible. Bilayered tablets were prepared using Ivabradine hydrochloride as the model drug and synthesized thiolated gums as mucoadhesive polymer. Tablets prepared using thiolated polymers in combination showed more swelling, mucoadhesion and residence time as compared to unmodified gums. Thiol modification controlled the release of the drug for 24 h and enhanced permeation of the drug up to 3 fold through porcine buccal mucosa as compared to tablets with unmodified gums. Thiolated polymer showed increased mucoadhesion and permeation, anticancer potential, controlled release and thus can be utilized as a novel excipient in formulation development.

10abuccal tablets10aenhanced permeation10aivabradine HCl10amucoadhesion10athiolated gums1 aMunot, Neha1 aKandekar, Ujjwala1 aRikame, Chaitali1 aPatil, Abhinandan1 aSengupta, Poulomi1 aUrooj, Shabana1 aBilal, Anusha uhttps://library.ncl.res.in/content/improved-mucoadhesion-permeation-and-vitro-anticancer-potential-synthesized-thiolated-acacia