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Bladder microenvironment actuated proteomotors with ammonia amplification for enhanced cancer treatment

药学学报:英文版 2023年第9期13卷 3862-3875页

作者： Hao Tian Juanfeng Ou Yong Wang Jia Sun Junbin Gao Yicheng Ye Ruotian Zhang Bin Chen Fei Wang Weichang Huang Huaan Li Lu Liu Chuxiao Shao Zhili Xu Fei Peng Yingfeng Tu NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui Central Laboratory of Lishui People’s HospitalThe Sixth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Department of Ultrasound Institute of Ultrasound in Musculoskeletal Sports MedicineGuangdong Second Provincial General HospitalGuangzhou 510317China School of Materials Science and Engineering Sun Yat-Sen UniversityGuangzhou 510275China

Enzyme-driven micro/nanomotors consuming in situ chemical fuels have attracted lots of attention for biomedical ***,motor systems composed by organism-derived organics that maximize the therapeutic efficacy of enzymatic products remain ***,swimming proteomotors based on biocompatible urease and human serum albumin are constructed for enhanced antitumor therapy via active motion and ammonia *** 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 *** 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 *** intravesical instillation,the proteomotors achieve longer bladder retention and thus significantly inhibit the growth of orthotopic bladder tumor in vivo without adverse *** envision that the as-developed swimming proteomotors with amplification of the product toxicity may be a potential platform for active cancer treatment.

关键词： Swimming proteomotors enhanced diffusion Glutamine synthetase Ammonia amplification Biocompatibility Penetration Retention Bladder microenvironment

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