Digital Repository

Development of l‑Tyrosine-Based Enzyme-Responsive Amphiphilic Poly(ester-urethane) Nanocarriers for Multiple Drug Delivery to Cancer Cells

Show simple item record

dc.contributor.author ALURI, RAJENDRA en_US
dc.contributor.author JAYAKANNAN, MANICKAM en_US
dc.date.accessioned 2022-06-13T04:29:21Z
dc.date.available 2022-06-13T04:29:21Z
dc.date.issued 2016-01 en_US
dc.identifier.citation Biomacromolecules, 18(1), 189-200. en_US
dc.identifier.issn 1525-7797 en_US
dc.identifier.uri https://doi.org/10.1021/acs.biomac.6b01476 en_US
dc.identifier.uri http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/7049
dc.description.abstract New classes of enzymatic-biodegradable amphiphilic poly­(ester-urethane)­s were designed and developed from l-tyrosine amino acid resources and their self-assembled nanoparticles were employed as multiple drug delivery vehicles in cancer therapy. The amine and carboxylic acid functional groups in l-tyrosine were converted into dual functional ester-urethane monomers and they were subjected to solvent free melt polycondensation with hydrophilic polyethylene glycols to produce comb-type poly­(ester-urethane)­s. The phenolic unit in the l-tyrosine was anchored with hydrophobic alkyl side chain to bring appropriate amphiphilicity in the polymer geometry to self-assemble them as stable nanoscaffolds in aqueous medium. The topology of the polymer was found to play a major role on the glass transition, crystallinity, and viscoelastic rheological properties of l-tyrosine poly­(ester-urethane)­s. The amphiphilic polymers were self-assembled as 200 ± 10 nm nanoparticles and they exhibited excellent encapsulation capabilities for anticancer drugs such as doxorubicin (DOX) and camptothecin (CPT). In vitro drug release studies revealed that the drug-loaded l-tyrosine nanoparticles were stable at extracellular conditions and they underwent enzymatic-biodegradation exclusively at the intracellular level to release the drugs. Cytotoxicity studies in the cervical cancer (HeLa) and normal WT-MEFs cell lines revealed that the nascent l-tyrosine nanoparticles were nontoxic, whereas the CPT and DOX drug-loaded polymer nanoparticles exhibited excellent cell killing in cancer cells. Confocal microscopic imaging confirmed the cellular internalization of drug-loaded nanoparticles. The drugs were taken up by the cells much higher quantity while delivering them from l-tyrosine nanoparticle platform compared to their free state. Flow cytometry analysis showed that the DOX-loaded polymer nanoscaffolds internalized the drugs 8–10× higher compared to free DOX. Both the synthesis of new classes of poly­(ester-urethane)­s via melt polycondensation approach and the enzyme-responsive drug delivery concept were accomplished for the first time. Thus, the present investigation is expected to open up new opportunities for l-tyrosine polymeric materials in biomaterial and thermoplastic applications. en_US
dc.language.iso en en_US
dc.publisher American Chemical Society en_US
dc.subject Chemistry en_US
dc.subject 2016 en_US
dc.title Development of l‑Tyrosine-Based Enzyme-Responsive Amphiphilic Poly(ester-urethane) Nanocarriers for Multiple Drug Delivery to Cancer Cells en_US
dc.type Article en_US
dc.contributor.department Dept. of Chemistry en_US
dc.identifier.sourcetitle Biomacromolecules en_US
dc.publication.originofpublisher Foreign en_US


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search Repository


Advanced Search

Browse

My Account