@article {49794,
	title = {Redox- and pH-responsive block copolymer nanocarriers with dual drug conjugation through dynamic covalent and hydrogen bonds},
	journal = {Journal of Applied Polymer Science},
	volume = {143},
	year = {2026},
	month = {MAR},
	pages = {e70205},
	type = {Article},
	abstract = {<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>
},
	keywords = {biodegradable, copolymers, DOX-conjugate, drug delivery systems, methotrexate, micelles, pH-responsive, redox-responsive},
	issn = {0021-8995},
	doi = {10.1002/app.70205},
	author = {Avhad, Shankarrao V. and Surapaneni, Sai Geetika and Purohit, Poorvi M. and Ambade, Ashootosh V.}
}
