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Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment
Huang, Xiaobei1; Mu, Ning2,3; Ding, Yuanfu4; Lam, Hou Wang4; Yue, Ludan4; Gao, Cheng4; Chen, Tunan2,3; Yuan, Zhen5; Wang, Ruibing4
2022-07-15
摘要Nanoparticles (NPs) modified with targeting ligands have often shown great potential in targeted drug delivery for tumor therapy. However, the clearance of NPs by the monocyte-phagocyte system (MPS) and the relatively low cellular uptake by tumor cells have significantly limited the antitumor efficacy of a variety of nanomedicines. Tumor microenvironment-mediated multidrug resistance also reduces the an-titumor efficacy of internalized nanomedicines. Herein, we developed an innovative nanomedicine for combined chemo-photodynamic therapy of melanoma through targeted drug delivery and significantly improved the cellular uptake of the nanomedicine through the charge-reversal phenomenon. An am-phiphilic platinum (IV)-polyethylenimine-chlorin e6 (Pt(IV)-PEI-Ce6) polymer was designed, prepared, and self-assembled into NPs (PPC) in an aqueous solution, and these NPs were subsequently coated with hyaluronic acid (HA) to afford PPC@HA. The surface-coated HA provided PPC with a negatively charged surface potential to reduce the clearance by the MPS during systemic circulation and enhanced the tar-geted delivery of PPC to CD44-overexpressing melanoma cells. Upon accumulation in the tumor site, hyaluronidase overexpressed in the tumor induced HA degradation to release the positively charged PPC, resulting in an increased internalization of PPC into tumor cells. Bioactive Pt(II) was released in response to high glutathione level in the tumor cells for effective tumor chemotherapy. Under 650 nm laser irradi-ation, Ce6 produced reactive oxygen species (ROS), thus driving photodynamic therapy. Finally, PPC@HA exhibited combined photodynamic-chemotherapeutic antitumor efficacy against the melanoma cells in mice.
关键词Photodynamic-chemotherapeutic therapy Pt(IV) prodrug Charge -reversal Targeted drug delivery Controlled drug release
DOI10.1016/j.actbio.2022.05.015
发表期刊ACTA BIOMATERIALIA
ISSN1742-7061
卷号147页码:356-365
通讯作者Chen, Tunan(ctn@tmmu.edu.cn) ; Yuan, Zhen(zhenyuan@um.edu.mo) ; Wang, Ruibing(rwang@um.edu.mo)
收录类别SCI
WOS记录号WOS:000829655400009
语种英语