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Explores a polymeric conjugate that enhances drug delivery effectiveness in cancer treatment, suggesting improved therapeutic options.
A linear-dendritic polymer has been explored as a drug delivery vehicle for cancer therapy. In this study, we successfully prepared a tumor microenvironment-responsive, dendronized and block poly[N-(2-hydroxypropyl) methacrylamide] (polyHPMA)-based copolymer-doxorubicin conjugate (pHPMA-block-pDendron-DOX) via two-step reversible addition-fragmentation chain transfer (RAFT) polymerization. The conjugate self-assembled into nanoparticles (NPs). Due to the presence of the Gly-Phe-Leu-Gly (GFLG) tetrapeptide and the hydrazone bond in the structure of the conjugate, cathepsin B-responsive degradation and pH-responsive drug release were realized within the tumor microenvironment. The NPs displayed a distinctive cytotoxic effect on 4T1 cells after internalization through endocytosis pathways. Significant improvements in the accumulation of doxorubicin (DOX) from the NPs were observed at the tumor site in a 4T1 murine breast cancer xenograft model, leading to promising anti-cancer effects. In addition, the side effects of DOX were significantly diminished in the NPs at a high dose. The prepared linear-dendritic conjugate could be used as an efficient and safe nanomedicine.
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Wang et al. (2026) studied this question.
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