Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles.
10.1016/j.apsb.2023.03.020
- Author:
Mei LU
1
;
Haonan XING
2
;
Wanxuan SHAO
1
;
Pengfei WU
1
;
Yuchuan FAN
1
;
Huining HE
3
;
Stefan BARTH
4
;
Aiping ZHENG
5
;
Xing-Jie LIANG
2
;
Yuanyu HUANG
1
Author Information
1. Advanced Research Institute of Multidisciplinary Science, School of Life Science, School of Medical Technology, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, Beijing 100081, China.
2. Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
3. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
4. South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine (IDM), Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
5. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
- Publication Type:Journal Article
- Keywords:
Antitumor synergism;
Combined cancer immunotherapy;
CompuSyn;
Extracellular vesicles;
Immune infiltration;
Immunogenic phototherapy;
RNA interference;
p21-activated kinase 4
- From:
Acta Pharmaceutica Sinica B
2023;13(9):3945-3955
- CountryChina
- Language:English
-
Abstract:
Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.
