02255nas a2200277   4500008004100000022001400041245012900055210006900184260000800253300001100261490000800272520131600280653001801596653001501614653001801629653002601647653001701673653001301690653001801703653002101721100002601742700002901768700002401797700002601821856013001847       2026                        eng d  a0021-899500aRedox- and pH-responsive block copolymer nanocarriers with dual drug conjugation through dynamic covalent and hydrogen bonds0 aRedox and pHresponsive block copolymer nanocarriers with dual dr  cMAR  ae702050 v1433 a<p>
	Loading of multiple drugs in a nanocarrier with high entrapment efficiency is important for combination therapy in cancer treatment. Here, a block copolymer comprising hydrophobic poly(epsilon-caprolactone) block with a defined number of pendent propargyl groups, polyethylene glycol monomethyl ether as a hydrophilic block, and a redox-responsive disulfide group at the block junction is synthesized using click chemistry and ring-opening polymerization (ROP). Benzaldehyde and thymine groups are introduced in the side chains for selective attachment of anti-cancer drugs, doxorubicin (DOX) and methotrexate (MTX), via the formation of pH-responsive imine linkage and hydrogen bonds, respectively. The drug-conjugated block copolymers are assembled into spherical micelles of &lt; 200 nm, and the preferential release of DOX and MTX in response to acidic pH and redox conditions is shown. At pH 5, DOX release was 59.5%, and MTX release was 40% compared to 13% and 12% at pH 7.4, whereas at pH 5 with 10 mM GSH, a DOX release of 81.5% was observed after 48 h. Cellular uptake of drug-conjugated micelles and their apoptosis compared to free DOX in the MDA-MB-231 breast cancer cells is demonstrated. Caveolae-mediated endocytosis was found to be the major pathway used by drug-loaded nanocarriers.</p>
10abiodegradable10acopolymers10aDOX-conjugate10adrug delivery systems10amethotrexate10amicelles10apH-responsive10aredox-responsive1 aAvhad, Shankarrao, V.1 aSurapaneni, Sai, Geetika1 aPurohit, Poorvi, M.1 aAmbade, Ashootosh, V.  uhttps://library.ncl.res.in/content/redox-and-ph-responsive-block-copolymer-nanocarriers-dual-drug-conjugation-through-dynamic