Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment.
10.1016/j.apsb.2023.02.016
- Author:
Hao TIAN
1
;
Juanfeng OU
1
;
Yong WANG
2
;
Jia SUN
1
;
Junbin GAO
1
;
Yicheng YE
1
;
Ruotian ZHANG
1
;
Bin CHEN
1
;
Fei WANG
1
;
Weichang HUANG
1
;
Huaan LI
1
;
Lu LIU
1
;
Chuxiao SHAO
3
;
Zhili XU
4
;
Fei PENG
5
;
Yingfeng TU
1
Author Information
1. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
2. Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
3. Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, Central Laboratory of Lishui People's Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China.
4. Department of Ultrasound, Institute of Ultrasound in Musculoskeletal Sports Medicine, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.
5. School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
- Publication Type:Journal Article
- Keywords:
Ammonia amplification;
Biocompatibility;
Bladder microenvironment;
Enhanced diffusion;
Glutamine synthetase;
Penetration;
Retention;
Swimming proteomotors
- From:
Acta Pharmaceutica Sinica B
2023;13(9):3862-3875
- CountryChina
- Language:English
-
Abstract:
Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical applications. However, motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain challenging. Herein, swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia amplification. By decomposing urea into carbon dioxide and ammonia, the designed proteomotors are endowed with self-propulsive capability, which leads to improved internalization and enhanced penetration in vitro. As a glutamine synthetase inhibitor, the loaded l-methionine sulfoximine further prevents the conversion of toxic ammonia into non-toxic glutamine in both tumor and stromal cells, resulting in local ammonia amplification. After intravesical instillation, the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse effects. We envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.
