期刊
ADVANCED FUNCTIONAL MATERIALS
卷 32, 期 51, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202208354
关键词
lysosome cell deaths; multimodal imaging; phototherapy; photothermal; renal clearance; self-assemblies
类别
资金
- National Natural Science Foundation of China [21874066]
- National Key R&D Program of China [2019YFA0709200]
- Key Research and Development Program of Jiangsu Province [BE2021373]
- Natural Science Foundation of Jiangsu Province [BK20200336]
- Fundamental Research Funds for Central Universities
- Program for Innovative Talents and Entrepreneur in Jiangsu
- Program B for Outstanding PhD Candidate of Nanjing University
This study developed a pH-responsive reversible self-assembled Cu2-xSe-BSA nanodrug that can be renal cleared and selectively targeted aggregated in cancer lysosomes, enhancing tumor accumulation and retention. Furthermore, the nanodrug also demonstrated enhanced photoacoustic imaging signal, photothermal therapy, and chemodynamic therapy capability.
Renal clearance is critical for nanodrug to avoid the long-term body retention-related side effects, while it is difficult to achieve efficient tumor accumulation and retention. The over-developed lysosomes in cancer cells have become an emerging target for more precise and effective cancer therapy. Herein, a pH-responsive reversible self-assembled Cu2-xSe-BSA, which can be renal cleared under neutral or basic conditions, is developed for selectively targeted aggregation in cancer lysosomes with enhanced tumor accumulation and retention. Moreover, the aggregation of Cu2-xSe-BSA can enhance the photoacoustic imaging signal, photothermal therapy, and chemodynamic therapy capability. Cu2-xSe-BSA accumulated in lysosomes cannot only induce lysosomes swelling, but also generate reactive oxygen species in situ, causing lysosomal membrane permeabilization and finally lysosomal cell death. Notably, the assembled Cu2-xSe-BSA can dissociate to be renal clearable after the treatments are completed and left the acid tumor microenvironment, being of great significance both in scientific research and clinical trial.
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