Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy.
10.1016/j.apsb.2022.07.023
- Author:
Zaigang ZHOU
1
;
Jiashe CHEN
2
;
Yu LIU
1
;
Chunjuan ZHENG
3
;
Wenjuan LUO
3
;
Lele CHEN
2
;
Shen ZHOU
2
;
Zhiming LI
2
;
Jianliang SHEN
1
Author Information
1. State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China.
2. Department of the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
3. School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
- Publication Type:Journal Article
- Keywords:
Hypoxia;
Mitochondrial oxidative phosphorylation;
Photodynamic immunotherapy;
Programmed death ligand-1;
Sorafenib;
Tumor vessel normalization
- From:
Acta Pharmaceutica Sinica B
2022;12(11):4204-4223
- CountryChina
- Language:English
-
Abstract:
As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.
