Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy.
10.1016/j.apsb.2022.06.008
- Author:
Jianjun CHENG
1
;
Haitian ZHAO
1
;
Bin LI
2
;
Hua ZHANG
3
;
Qianyu ZHAO
1
;
Shiyao FU
1
;
Ying HAN
1
;
Weihong LU
1
;
Jiahua SHI
4
;
Xin YANG
1
Author Information
1. School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China.
2. Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
3. School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China.
4. Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, Henan University, Kaifeng 475004, China.
- Publication Type:Journal Article
- Keywords:
Betulinic acid;
Cancer immunotherapy;
Chemotherapeutic dormancy;
Nano-immunostimulants;
Natural small molecule;
Photodynamic therapy;
Pro-drug;
Self-assembly
- From:
Acta Pharmaceutica Sinica B
2023;13(2):879-896
- CountryChina
- Language:English
-
Abstract:
Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.
