Therapeutic and responsive release mechanisms of polymer drug conjugates with diverse polymer skeletons

Polymer-drug conjugates (PDCs) have emerged as an advanced strategy in the drug delivery. The conjugation of therapeutic or diagnostic agents to polymers, such as polyurethane, polyester, RAFT-based polymers, and poly(amino acid)s, presents several advantages, including enhanced drug solubilization, controlled release, reduced immunogenicity, prolonged circulation, improved safety, and increased efficacy. Recent research has focused extensively on engineering efficient tumor microenvironment (TME)-responsive PDCs, leading to significant advancements in cancer diagnosis and therapy. This review discusses the rational design, mechanisms of responsive release, physicochemical properties, and recent developments in various polymer systems for PDCs. We categorize PDCs based on their skeletal designs, including polyurethane, polyester, RAFT polymers, and polyamino acids. Additionally, we emphasize the TME responsiveness of PDCs, highlighting its critical role in various tumor therapies. Finally, we address the current challenges faced by PDCs and offer perspectives for future research, providing insights into the utility and potential of this technology. We hope this review serves as a valuable resource for the selection and optimization of PDCs, facilitating their future applications in cancer therapeutics.