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Not AvSelf-assembled polymeric micelles formed from amphiphilic block copolymers offer a promising strategy for enhanced drug delivery due to their biocompatibility and controlled release. However, challenges such as their poor colloidal stability under diluted conditions and degradation during storage and circulation limit their further applications. To address these issues, we developed a straightforward method for constructing cross-linked polycarbonate micelles that enhance stability while allowing for controlled stimuli-responsive drug delivery. By utilizing disulfide-based cross-linking and covalent conjugation of the anticancer drug, our approach maintains micelle integrity and extremely high drug loading over extended periods as well as the superior control of triggered drug release compared to non-cross-linked versions, demonstrating enhanced stability in complex biological environments and improved anticancer efficacy, presenting a novel platform for stable polymer–drug conjugate nanocarriers, holding significant therapeutic potential for targeted cancer treatment.
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This content will become publicly available on November 10, 2026
Glutathione-Responsive Polyhomocysteine Derivatives with Ultralow Toxicity toward Therapeutic Delivery
Not AvaDisulfide-containing synthetic polypeptides hold significant promise as biodegradable and biocompatible carriers for controlled drug and gene delivery, enabling triggered therapeutic release with reduced cytotoxicity. However, disulfide incorporation remains challenging, whether through direct polymerization of disulfide-containing monomers or postpolymerization modification. In this work, we present an innovative and simple strategy to incorporate disulfide bonds into polypeptides using ring-opening polymerization of the N-carboxyanhydride of homocysteine, a thiol-containing amino acid. The polymerization was well-controlled, yielding repeating units up to 100 with narrow dispersity. The pendant side chains were readily converted into various GSH-responsive moieties, including anionic, neutral, zwitterionic, and cationic groups, as well as therapeutic agents toward a wide range of biomedical applications. The drug-loaded amphiphilic polymer-drug conjugates displayed triggered release of intact drug and potent anticancer activities. Furthermore, cationic polyhomocysteine derivatives effectively delivered siRNA, eGFP mRNA, and more complex CRISPR components with extremely low cytotoxicity and excellent transfection efficiency.ilable
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- Award ID(s):
- 2238812
- PAR ID:
- 10656387
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- Biomacromolecules
- Volume:
- 26
- Issue:
- 11
- ISSN:
- 1525-7797
- Page Range / eLocation ID:
- 7470 to 7483
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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