Yu Ying, Song Meiyu, Chen Cailing, Du Yangyang, Li Chunguang, Han Yu, Yan Fei, Shi Zhan, Feng Shouhua
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), International Research Center for Chemistry-Medicine Joint Innovation, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
Advanced Membranes and Porous Materials Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
ACS Nano. 2020 Aug 25;14(8):10688-10703. doi: 10.1021/acsnano.0c05332. Epub 2020 Aug 17.
Photothermal therapy (PTT) is an emerging therapeutic strategy in the treatment of cancer; however, a critical challenge remains in the rational design of synergistic nanoparticles as a potential photothermal transduction agent that can effectively enhance the therapeutic outcome of PTT for tumor ablation. Herein, we rationally designed, developed, and characterized hollow-structured CuS nanoparticles composited with carbon dots (CuSCDs), which demonstrated excellent photothermal conversion efficiency under a 808 nm laser irradiation with enhanced biocompatibility and reduced toxicity. Following coating with a macrophage membrane hybridized with T7 peptide on the surface of the proteasome inhibitor loaded CuSCD, CuSCDB@MMT7 exhibited targeted specificity to cancer cells with the characteristics of immunity escaping and enhanced transferrin receptor-mediated endocytosis. Predominantly, CuSCDB@MMT7-triggered PTT exhibited the accumulation of the polyubiquitinated tumor suppressor protein that is heat stabilized under NIR induced hyperthermia, facilitating augmented tumor cell apoptosis and the attenuated metastasis. This study provides a proof-of-concept for the proteasome inhibitor-loaded CuS/carbon dot nanocomposite-PTT strategy and highlights a promising therapeutic strategy for realizing enhanced therapeutic outcomes for effective clinical cancer therapy.
光热疗法（PTT）是癌症治疗中一种新兴的治疗策略；然而，在合理设计协同纳米粒子作为潜在的光热转导剂方面，仍然存在一个关键挑战，这种光热转导剂能够有效提高PTT对肿瘤消融的治疗效果。在此，我们合理设计、开发并表征了与碳点复合的中空结构硫化铜纳米粒子（CuSCDs），其在808nm激光照射下表现出优异的光热转换效率，同时具有增强的生物相容性和降低的毒性。在负载蛋白酶体抑制剂的CuSCD表面用与T7肽杂交的巨噬细胞膜进行包被后，CuSCDB@MMT7对癌细胞表现出靶向特异性，具有免疫逃逸和增强转铁蛋白受体介导的内吞作用的特点。主要地，CuSCDB@MMT7触发的PTT表现出多聚泛素化肿瘤抑制蛋白的积累；该蛋白在近红外诱导的热疗下是热稳定的，促进了肿瘤细胞凋亡的增加和转移的减弱。本研究为负载蛋白酶体抑制剂的硫化铜/碳点纳米复合材料-PTT策略提供了概念验证，并突出了一种有前景的治疗策略，以实现增强的治疗效果用于有效的临床癌症治疗。
