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用于联合肿瘤靶向化疗和光动力免疫治疗的近红外光对核靶向铂纳米颗粒的光还原作用

Photo-Reduction with NIR Light of Nucleus-Targeting Pt Nanoparticles for Combined Tumor-Targeted Chemotherapy and Photodynamic Immunotherapy.

作者信息

Wei Dengshuai, Huang Yun, Wang Bin, Ma Lili, Karges Johannes, Xiao Haihua

机构信息

Beijing National Laboratory for Molecular Science, State Key Laboratory of Polymer Physical and Chemistry, Institute of Chemistry Chinese Academy of Science, Beijing, 100190, China.

University of Chinese Academy of Sciences, Beijing, 100049, China.

出版信息

Angew Chem Int Ed Engl. 2022 May 9;61(20):e202201486. doi: 10.1002/anie.202201486. Epub 2022 Mar 16.

Abstract

The development of Pt prodrugs which are selectively reduced within cancerous cells into their Pt therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep-seated or large tumors is limited. To overcome this limitation, herein, the example of Pt -functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self-assemble into nanoparticles was functionalized with Pt complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer-targeting peptides. Upon irradiation, the Pt center is reduced to Pt and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple-negative breast cancer tumor inside a mouse model.

摘要

在过去十年中,能够在癌细胞内选择性还原为其具有治疗活性的铂物种的铂前药的开发受到了越来越多的关注。尽管最近有研究进展,但大多数研究的化合物是用紫外线或蓝光激发的。由于在这些波长下光穿透深度较低,深部或大型肿瘤的治疗受到限制。为了克服这一限制,本文报道了在808 nm近红外区域可被激发的铂功能化纳米颗粒的实例。可自组装成纳米颗粒的聚合物主链用用于化疗的铂配合物、用于光动力免疫治疗的光敏剂和靶向细胞核/癌症的肽进行功能化。照射后,铂中心还原为铂,轴向配位的配体被释放,呈现出多模态治疗。纳米颗粒在肿瘤组织中选择性积累的同时,还展示了在小鼠模型中根除三阴性乳腺癌肿瘤的能力。

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