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• W4366752890 abstract "The combination of chemotherapy and photodynamic therapy (PDT) has the potential to complement single-drug therapies, but chemotherapeutic agents and photosensitizers often have compromised therapeutic efficacies and strong toxic effects. In this study, we exploited nanotechnology to address this challenge by utilizing heparin as a carrier for co-delivery of chemotherapeutic drugs and photosensitizers for synergistic cancer therapy. Specifically, heparin-paclitaxel (HP-PTX) and heparin-pyropheophorbide-a (HP-Ppa) were synthesized by attaching paclitaxel (PTX), a small molecular chemotherapeutic drug, through a reactive oxygen species (ROS)-responsive linker and Ppa, a photosensitizer, to heparin, respectively. Two conjugates were co-assembled into a nanomedicine, HP-PP nanoparticles (NPs), for controllable co-delivery of Ppa and PTX into tumor cells. HP-PP NPs significantly enhanced the in vitro stability of HP-Ppa and the photostability of Ppa, and the synergistic actions of chemotherapy and PDT were confirmed by both in vitro and in vivo antitumor studies. Notably, HP-PP NPs enhanced tumor accumulation of Ppa up to 11-fold and the treatment of 4T1 tumor-bearing mice with HP-PP NPs resulted in a tumor growth inhibition of 98.1% without systemic toxicity. The strategy of co-assembly of heparin conjugates may offer great potential in enhancing the efficacy of combination therapy. STATEMENT OF SIGNIFICANCE: We proposed a nano-delivery system, HP-PP NPs, which was constructed by co-assembly of heparin-paclitaxel (HP-PTX) and heparin-pyropheophorbide-a (HP-Ppa), to co-deliver PTX and Ppa for synergistic cancer therapy. HP-PP NPs enhanced the photostability and the in vitro stability of Ppa and HP-Ppa, and induced greater cytotoxicity than HP-PTX NPs or HP-Ppa NPs. This co-delivery system displays enhanced tumor accumulation and has a remarkable synergistic antitumor effect with a tumor growth inhibition of 98.1%." @default.
• W4366752890 created "2023-04-24" @default.
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• W4366752890 date "2023-07-01" @default.
• W4366752890 modified "2023-10-16" @default.
• W4366752890 title "Stimuli-responsive heparin-drug conjugates co-assembled into stable nanomedicines for cancer therapy" @default.
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• W4366752890 doi "https://doi.org/10.1016/j.actbio.2023.04.016" @default.
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