Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy.
10.1016/j.apsb.2021.07.001
- Author:
Shuangquan GOU
1
;
Nanxi CHEN
2
;
Xiaoai WU
3
;
Menghang ZU
2
;
Shixiong YI
2
;
Binwu YING
4
;
Fangyin DAI
2
;
Bowen KE
1
;
Bo XIAO
2
Author Information
1. Laboratory of Anesthesiology & Critical Care Medicine, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.
2. State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.
3. Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
4. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
Cancer;
Chemotherapy;
Mitochondrial targeting;
Nanotheranostic;
Oxygen self-generation;
Phototherapy;
Quadruple responsibility;
Silk fiborin
- From:
Acta Pharmaceutica Sinica B
2022;12(1):406-423
- CountryChina
- Language:English
-
Abstract:
Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (-25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.
