Mitochondria-Mediated HSP Inhibition Strategy for Enhanced Low-Temperature Photothermal Therapy

• Published in: ACS applied materials & interfaces 2023-06, Vol.15 (22), p.26252-26262
• Main Authors: Liu, Wenting, Di, Jianhao, Ma, Yan, Wang, Shuo, Meng, Meng, Yin, Yongmei, Xi, Rimo, Zhao, Xiujie
• Format: Article
• Language: English
• Subjects: Biological and Medical Applications of Materials and Interfaces; energy; heat stress; immunohistochemistry; mitochondria; nanoparticles; photothermotherapy; thermosensitivity; Western blotting
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.3c00870

Low-temperature photothermal therapy (PTT) has the advantage of causing less damage to normal tissues and has attracted great attention in recent years. However, the efficacy of low-temperature PTT is restricted by the overexpression of heat shock proteins (HSPs), specifically HSP70 and HSP90. Inhibiting the function of these HSPs is a major strategy used in the development of new cancer therapies. Herein, we designed four T780T-containing thermosensitive nanoparticles to interrupt the energy supply for HSP expression using their TPP-based mitochondrial targeting action. The reversal behavior of the nanoparticles on the gambogic acid (GA)-induced compensatory increase of HSP70 was investigated in vitro by Western blot and in vivo by immunohistochemistry. The in vivo anticancer efficacy of the low-temperature PTT based on these thermosensitive nanoparticles was also systematically examined. The design proposes for the first time to utilize and elucidate the mechanism of the mitochondrial targeting of T780T-containing NPs in synergy with the HSP90 inhibition of GA to achieve an effective low-temperature PTT. This work not only provides a novel pathway for the dual inhibition of HSP70 and HSP90 but also opens up a new approach for low-temperature PTT of tumors.