Citation: Fujun Yang, Qingyu Ji, Rui Liao, Shumeng Li, Yuequan Wang, Xuanbo Zhang, Shenwu Zhang, Haotian Zhang, Qiming Kan, Jin Sun, Zhonggui He, Bingjun Sun, Cong Luo. Precisely engineering a dual-drug cooperative nanoassembly for proteasome inhibition-potentiated photodynamic therapy[J]. Chinese Chemical Letters, ;2022, 33(4): 1927-1932. doi: 10.1016/j.cclet.2021.11.056 shu

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

Fujun Yang ^a ,
Qingyu Ji ^a ,
Rui Liao ^a ,
Shumeng Li ^a ,
Yuequan Wang ^a ,
Xuanbo Zhang ^a ,
Shenwu Zhang ^a ,
Haotian Zhang ^b ,
Qiming Kan ^b ,
Jin Sun ^a ,
Zhonggui He ^a ,
Bingjun Sun ^{a, *,} ,
Cong Luo ^{a, *,}

a.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

sunbingjun_spy@sina.com

luocong@syphu.edu.cn

Received Date: 7 September 2021
Revised Date: 15 November 2021
Accepted Date: 16 November 2021
Available Online: 24 November 2021

Figures(5)

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.
- Bortezomib,
- Pyropheophorbide a,
- Precisely cooperative nanoassembly,
- Proteasome inhibition,
- Photodynamic therapy,
- Multimodal cancer therapy
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