酶驱动的以原位化学燃料为消耗物的微/纳米马达在生物医学应用中受到了广泛关注。然而，由生物源性有机物组成的马达系统，能够最大化酶产物的治疗效果仍然具有挑战性。本文构建了基于生物相容性尿酶和人血清白蛋白的游泳蛋白马达，通过主动运动和氨增强来增强抗肿瘤治疗效果。通过将尿素分解为二氧化碳和氨，设计的蛋白马达具有自驱动能力，从而在细胞外实现了改进的内吞和增强的穿透性。作为谷氨酰胺合成酶抑制剂，装载的L-甲硫氧嘧啶进一步阻止了毒性氨转化为非毒性谷氨酰胺的过程，在肿瘤和基质细胞中实现了局部氨增强。经过膀胱灌洗，蛋白马达实现了更长时间的膀胱滞留，从而在体内显著抑制了原位膀胱肿瘤的生长，而无不良反应。我们预计，通过增强产物毒性的游泳蛋白马达可能是一种潜在的主动式癌症治疗平台。© 2023中国药学会和中国医学科学院药物研究所。Elsevier B.V.负责制作与托管。

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.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.