Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/3848
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dc.contributor.authorAluri, Rajendraen_US
dc.contributor.authorSaxena, Sonashreeen_US
dc.contributor.authorJoshi, Dheeraj Chandraen_US
dc.contributor.authorJAYAKANNAN, MANICKAMen_US
dc.date.accessioned2019-09-09T11:25:51Z
dc.date.available2019-09-09T11:25:51Z
dc.date.issued2018-04en_US
dc.identifier.citationBiomacromolecules, 19(6), 2166-2181.en_US
dc.identifier.issn1525-7797en_US
dc.identifier.issn1526-4602en_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/3848-
dc.identifier.urihttps://doi.org/10.1021/acs.biomac.8b00334en_US
dc.description.abstractMultistimuli-responsive l-tyrosine-based amphiphilic poly(ester-urethane) nanocarriers were designed and developed for the first time to administer anticancer drugs in cancer tissue environments via thermoresponsiveness and lysosomal enzymatic biodegradation from a single polymer platform. For this purpose, multifunctional l-tyrosine monomer was tailor-made with a PEGylated side chain at the phenolic position along with urethane and carboxylic ester functionalities. Under melt dual ester-urethane polycondensation, the tyrosine monomer reacted with diols to produce high molecular weight amphiphilic poly(ester-urethane)s. The polymers produced 100 ± 10 nm spherical nanoparticles in aqueous medium, and they exhibited thermoresponsiveness followed by phase transition from clear solution into a turbid solution in heating/cooling cycles. Variable temperature transmittance, dynamic light scattering, and 1H NMR studies revealed that the polymer chains underwent reversible phase transition from coil-to-expanded chain conformation for exhibiting the thermoresponsive behavior. The lower critical solution temperature of the nanocarriers was found to correspond to cancer tissue temperature (at 42–44 °C), which was explored as an extracellular trigger (stimuli-1) for drug delivery through the disassembly process. The ester bond in the poly(ester-urethane) backbones readily underwent enzymatic biodegradation in the lysosomal compartments that served as intracellular stimuli (stimuli-2) to deliver drugs. Doxorubicin (DOX) and camptothecin (CPT) drug-loaded polymer nanocarriers were tested for cellular uptake and cytotoxicity studies in the normal WT-MEF cell line and cervical (HeLa) and breast (MCF7) cancer cell lines. In vitro drug release studies revealed that the polymer nanoparticles were stable under physiological conditions (37 °C, pH 7.4) and they exclusively underwent disassembly at cancer tissue temperature (at 42 °C) and biodegradation by lysosomal-esterase enzyme to deliver 90% of DOX and CPT. Drug-loaded polymer nanoparticles exhibited better cytotoxic effects than their corresponding free drugs. Live cell confocal microscopy imaging experiments with lysosomal tracker confirmed the endocytosis of the polymer nanoparticles and their biodegradation in the lysosomal compartments in cancer cells. The increment in the drug content in the cells incubated at 42 °C compared to 37 °C supported the enhanced drug uptake by the cancer cells under thermoresponsive stimuli. The present work creates a new platform for the l-amino acid multiple-responsive polymer nanocarrier platform for drug delivery, and the proof-of-concept was successfully demonstrated for l-tyrosine polymers in cervical and breast cancer cells.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.subjectMultistimuli-Responsiveen_US
dc.subjectAmphiphilic Poly ester-urethaneen_US
dc.subjectNanoassemblies Baseden_US
dc.subjectTyrosine for Intracellular Drugen_US
dc.subjectDelivery Cancer Cellsen_US
dc.subject2018en_US
dc.titleMultistimuli-Responsive Amphiphilic Poly(ester-urethane) Nanoassemblies Based on l-Tyrosine for Intracellular Drug Delivery to Cancer Cellsen_US
dc.typeArticleen_US
dc.contributor.departmentDept. of Chemistryen_US
dc.identifier.sourcetitleBiomacromoleculesen_US
dc.publication.originofpublisherForeignen_US
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