4.7 Article

Precisely engineering a dual-drug cooperative nanoassembly for proteasome inhibition-potentiated photodynamic therapy

Journal

CHINESE CHEMICAL LETTERS
Volume 33, Issue 4, Pages 1927-1932

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cclet.2021.11.056

Keywords

Bortezomib; Pyropheophorbide a; Precisely cooperative nanoassembly; Proteasome inhibition; Photodynamic therapy; Multimodal cancer therapy

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This study presents a facile dual-drug nanoassembly that enhances the efficacy of photodynamic therapy by inhibiting the proteasome. The engineered nanoassembly demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, and favorable stability and enrichment.
Photodynamic therapy (PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species (ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway (UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib (BTZ, a proteasome inhibitor) and pyropheophorbide a (PPa) for proteasome inhibition-mediated PDT sensitization. The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

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