Issue 17, 2023

Tumor-targeted AIE polymeric micelles mediated immunogenic sonodynamic therapy inhibits cancer growth and metastasis

Abstract

Aggregation-induced emission luminogens (AIEgens) exhibit potent sonosensitivity in nanocarriers compared with conventional organic sonosensitizers owing to the strong fluorescence emission in the aggregated state. However, the premature drug leakage and ineffective tumor targeting of current AIE nanosonosensitizers critically restrict their clinical applications. Here, an AIEgen-based sonosensitizer (AIE/Biotin-M) with excellent sonosensitivity was developed by assembling salicylaldazine-based amphiphilic polymers (AIE-1) and 4T1 tumor-targeting amphiphilic polymers (DSPE-PEG-Biotin) for the effective delivery of salicylaldazine to 4T1 tumor tissues, aiming to mediate immunogenic SDT. In vitro, AIE/Biotin-M were highly stable and generated plentiful singlet oxygen (1O2) under ultrasound (US) irradiation. After AIE/Biotin-M targeted accumulation in the tumor, upon US irradiation, the generation of 1O2 not only led to cancer cell death, but also elicited a systemically immune response by causing the immunogenic cell death (ICD) of cancer cells. In addition to mediating SDT, AIE/Biotin-M could chelate and reduce Fe3+, Cu2+ and Zn2+ by salicylaldazine for inhibiting neovascularization in tumor tissues. Ultimately, AIE/Biotin-M systemically inhibited tumor growth and metastasis upon US irradiation. This study presents a facile approach to the development of AIE nanosonosensitizers for cancer SDT.

Graphical abstract: Tumor-targeted AIE polymeric micelles mediated immunogenic sonodynamic therapy inhibits cancer growth and metastasis

Supplementary files

Article information

Article type
Paper
Submitted
01 Feb 2023
Accepted
04 Apr 2023
First published
17 Apr 2023

Nanoscale, 2023,15, 8006-8018

Tumor-targeted AIE polymeric micelles mediated immunogenic sonodynamic therapy inhibits cancer growth and metastasis

K. Deng, Y. Yu, Y. Zhao, J. Li, K. Li, H. Zhao, M. Wu and S. Huang, Nanoscale, 2023, 15, 8006 DOI: 10.1039/D3NR00473B

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