期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 590, 期 -, 页码 290-300出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2021.01.052
关键词
Heat shock protein 90; Hsp-90 inhibitor; Synergistic PTT and PDT; Multimodal therapy
资金
- National Natural Science Foundation of China [U1803283, 21878249, 22078049]
- Project of Science and Technology of Social Development in Shaanxi Province [2018JM2008]
- key technique improvement of Xinjiang Licorice planting and quality control of Xinjiang Production & Construction Corps [2018AB012]
This study explores a treatment strategy combining photothermal therapy and chemotherapy to promote apoptosis in cancer cells by inhibiting the overexpression of Hsp-90 and survivin.
The proangiogenic protein, survivin, is a client protein for heat shock protein 90 (Hsp-90), whose overexpression is induced by photodynamic therapy (PDT), leading to the inhibition of capase-9 and the blockage of apoptosis. The overexpression of Hsp-90 in cancer cells can rapidly acquire thermoresistance during photothermal therapy (PTT), leading to insufficient apoptosis, increased cell viability, and tumor recurrence. A potential approach to block the PTT-induced overexpression of Hsp-90 and the overexpression of survivin is developed by using an Hsp-90 inhibitor and anticancer agent, namely, geldanamycin (GM). These inhibitors also develop a mild-temperature PTT strategy to reach synergistic PDT and PTT efficiency. Thus, Cy7-SQ is designed by a covalent disulfide linkage between a photothermal agent (i.e., canine dye 7 [Cy7]) and a photosensitizer (i.e., squaraine dye [SQ]) for the improved photostability and thermal stability of Cy7 and SQ. The cleavage of the Cy7-SQ linkage by glutathione in a tumor microenvironment increases the efficiency of synergistic PDT and PTT. In the current study, bovine serum albumin (BSA)/Cy7-SQ/GM nanoparticles are developed through the self-assembly of BSA, Cy7-SQ, and GM to accelerate the apoptosis of cancer cells via near-infrared (NIR) laser irradiation, thus realizing Hsp-90-regulated synergistic PDT/PTT combined with chemotherapy. (c) 2021 Elsevier Inc. All rights reserved.
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