Liu Kunpeng, Jiao Binbin, Zhang Guan, Gan Zhihua, Lai Shicong, Ding Zhenshan, Yu Qingsong
The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
J Control Release. 2025 Aug 10;384:113905. doi: 10.1016/j.jconrel.2025.113905. Epub 2025 May 29.
Bladder cancer remains a significant clinical challenge, necessitating the development of innovative therapeutic strategies. Recent advancements have highlighted the potential of reactive oxygen species (ROS)-responsive drug delivery systems in cancer therapy. In this study, we introduce a novel treatment approach utilizing a ROS-responsive camptothecin (CPT) prodrug encapsulated within a chitosan nanocarrier, named CACPT. Cinnamaldehyde (CA), acting as a ROS generator, forms thioketal bonds with CPT to create a prodrug that responds selectively to the elevated ROS levels within the tumor microenvironment. Upon exposure to high ROS conditions, these thioketal bonds are cleaved, resulting in the simultaneous release of CPT and CA. The liberated CA further enhances ROS production, establishing a positive feedback loop that amplifies the therapeutic effect. The use of amphiphilic chitosan nanocarriers enhances the retention and penetration of the prodrug within bladder tissue, optimizing its therapeutic potential. Our experimental findings demonstrate that this self-enhanced ROS-responsive release promotes increased cellular uptake and significantly enhances the anticancer efficacy of CACPT. These results position CACPT as a promising candidate for intravesical therapy in bladder cancer, potentially overcoming current limitations in treatment options. The innovative combination of ROS-responsive mechanisms and chitosan nanocarriers represents a paradigm shift in bladder cancer therapeutics, offering a multifaceted approach with substantial promise for clinical translation.
膀胱癌仍然是一个重大的临床挑战，因此需要开发创新的治疗策略。最近的进展突出了活性氧（ROS）响应性药物递送系统在癌症治疗中的潜力。在本研究中，我们引入了一种新颖的治疗方法，利用包裹在壳聚糖纳米载体中的ROS响应性喜树碱（CPT）前药，命名为CACPT。肉桂醛（CA）作为ROS生成剂，与CPT形成硫代缩酮键以创建一种前药，该前药对肿瘤微环境中升高的ROS水平具有选择性响应。在暴露于高ROS条件下时，这些硫代缩酮键被裂解，导致CPT和CA同时释放。释放的CA进一步增强ROS的产生，建立一个正反馈回路，放大治疗效果。两亲性壳聚糖纳米载体的使用增强了前药在膀胱组织中的保留和渗透，优化了其治疗潜力。我们的实验结果表明，这种自我增强的ROS响应性释放促进了细胞摄取的增加，并显著增强了CACPT的抗癌功效。这些结果使CACPT成为膀胱癌膀胱内治疗的有希望的候选者，有可能克服当前治疗选择中的局限性。ROS响应机制和壳聚糖纳米载体的创新组合代表了膀胱癌治疗学的范式转变，提供了一种具有临床转化巨大潜力的多方面方法。
