TY - JOUR
T1 - Bortezomib-Encapsulated CuS/Carbon Dots Nanocomposites for Enhanced Photothermal Therapy via Stabilization of Polyubiquitinated Substrates in the Proteasomal Degradation Pathway
AU - Yu, Ying
AU - Song, Meiyu
AU - Chen, Cailing
AU - Du, Yangyang
AU - Li, Chunguang
AU - Han, Yu
AU - Yan, Fei
AU - Shi, Zhan
AU - Feng, Shouhua
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This work was supported by the National Natural Science Foundation of China (NSFC; nos. 81870117, 21771077, 21771084 and 21621001), the National Key Research and Development Program of China (no. 2016YFB0701100), the 111 project (no. B17020), and the Jilin Province Science and Technology Development Plan (20190201252JC). The authors also gratefully acknowledge the financial support by Program for JLU Science and Technology Innovative Research Team (JLUSTIRT).
PY - 2020/8/11
Y1 - 2020/8/11
N2 - 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 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 (CuSCD), which demonstrated excellent photothermal conversion efficiency under 808 nm laser irradiation with enhanced biocompatibility and reduced toxicity. Following coating macrophage membrane hybridized with T7 peptide on the surface of proteasome inhibitor loaded CuSCD, CuSCDB@MMT7 exhibited targeted specificity to cancer cells with the characteristics of immune escaping and enhanced transferrin receptor-mediated endocytosis. Predominantly, CuSCDB@MMT7-triggered PTT exhibited the accumulation of 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 dots nanocomposites-PTT strategy, and highlights a promising therapeutic strategy for realizing enhanced therapeutic outcomes for effective clinical cancer therapy.
AB - 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 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 (CuSCD), which demonstrated excellent photothermal conversion efficiency under 808 nm laser irradiation with enhanced biocompatibility and reduced toxicity. Following coating macrophage membrane hybridized with T7 peptide on the surface of proteasome inhibitor loaded CuSCD, CuSCDB@MMT7 exhibited targeted specificity to cancer cells with the characteristics of immune escaping and enhanced transferrin receptor-mediated endocytosis. Predominantly, CuSCDB@MMT7-triggered PTT exhibited the accumulation of 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 dots nanocomposites-PTT strategy, and highlights a promising therapeutic strategy for realizing enhanced therapeutic outcomes for effective clinical cancer therapy.
UR - http://hdl.handle.net/10754/664618
UR - https://pubs.acs.org/doi/10.1021/acsnano.0c05332
U2 - 10.1021/acsnano.0c05332
DO - 10.1021/acsnano.0c05332
M3 - Article
C2 - 32790339
SN - 1936-0851
JO - ACS Nano
JF - ACS Nano
ER -
