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Proteolysis-targeting chimera (PROTAC) has emerged as a groundbreaking therapeutic strategy by hijacking the endogenous ubiquitin proteasome system (UPS) for targeted protein degradation. These heterobifunctional molecules recruit E3 ligases to recognize the protein of interest (POI) and facilitate its ubiquitination, leading to subsequent proteasomal degradation. Compared to conventional protein inhibitors, PROTACs offer a broader range of target degradation and remain effective even against proteins with drug-resistant mutations. Moreover, PROTACs function in a catalytic manner to degrade POIs, allowing for significantly lower administration dosages. In recent years, PROTACs have shown great promise in cancer therapy due to their high efficiency and broad applicability. However, their clinical applications remain challenging due to low bioavailability, limited tumor-targeting ability, and potential side effects. Utilizing nanomedicine for the delivery of PROTACs offers a promising strategy to enhance bioavailability, improve tumor selectivity, and minimize toxicity, thereby advancing their applications in cancer treatment. In this review, we outline the fundamental design principles of PROTACs, summarize the latest progress of nanomedicines from molecular design to drug delivery for improved tumor treatment, introduce PROTAC-based combination therapies and emerging design strategies, and discuss current challenges and future prospects of PROTAC nanomedicines toward clinical translation. 

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.