Zhang Yixun, Liang Zhenguo, Tan Zeheng, Lin Jundong, Jiang Xinqing, Zhou Xin, Zhuo Yangjia, Zou Fen, Yang Ronghua, Zhong Weide, Yang Huikang
Department of Burn and Plastic Surgery, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, China.
Guangdong Provincial Key Laboratory of Urology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510230, China.
ACS Omega. 2025 Jun 4;10(23):24601-24617. doi: 10.1021/acsomega.5c01372. eCollection 2025 Jun 17.
Prostate cancer (PCa) remains a significant challenge in oncology due to its complex pathogenesis and resistance to conventional therapies. By leveraging bioinformatics-guided insights, we identified folate hydrolase 1 (FOLH1) as a crucial biomarker with overexpression in various cancers, particularly PCa. Therefore, we prepared folate receptor-targeted reactive oxygen species (ROS)-responsive dextran--poly-(propylene sulfide) nanoparticles to enhance targeted therapeutic efficacy against PCa. The block copolymer was achieved using Cu-(I)-catalyzed "click" chemistry, followed by the successful conjugation of folic acid (FA). Characterization confirmed the nanoparticles' ability to encapsulate doxorubicin (Dox) and respond to ROS, releasing the drug under oxidative conditions. In vitro studies demonstrated enhanced cellular uptake, increased ROS production, and superior cytotoxicity of FA-Dex--PPS-Dox in PC3 cells compared to free Dox and nontargeted Dex--PPS-Dox nanoparticles. Furthermore, FA-Dex--PPS-Dox significantly inhibited tumor cell migration and invasion, emphasizing its potential for comprehensive cancer therapy. In vivo efficacy was assessed using a PC3 tumor model, where FA-Dex--PPS-Dox notably reduced tumor volume and weight, with histological analyses confirming enhanced apoptosis and reduced cell proliferation. These findings underscore the promising potential of FA-Dex--PPS-Dox in providing a targeted, ROS-responsive therapeutic strategy for prostate cancer.
前列腺癌（PCa）由于其复杂的发病机制和对传统疗法的耐药性，仍然是肿瘤学领域的一项重大挑战。通过利用生物信息学指导的见解，我们确定叶酸水解酶1（FOLH1）是一种关键的生物标志物，在各种癌症，特别是前列腺癌中过度表达。因此，我们制备了叶酸受体靶向的活性氧（ROS）响应性葡聚糖-聚（硫化丙烯）纳米颗粒，以增强对前列腺癌的靶向治疗效果。通过铜（I）催化的“点击”化学实现了嵌段共聚物的合成，随后成功地偶联了叶酸（FA）。表征证实了纳米颗粒具有包封阿霉素（Dox）并对ROS作出响应的能力，在氧化条件下释放药物。体外研究表明，与游离Dox和非靶向的葡聚糖-聚（硫化丙烯）-阿霉素纳米颗粒相比，FA-Dex-聚（硫化丙烯）-阿霉素在PC3细胞中具有增强的细胞摄取、增加的ROS产生和更高的细胞毒性。此外，FA-Dex-聚（硫化丙烯）-阿霉素显著抑制肿瘤细胞的迁移和侵袭，突出了其在综合癌症治疗中的潜力。使用PC3肿瘤模型评估体内疗效，其中FA-Dex-聚（硫化丙烯）-阿霉素显著减小了肿瘤体积和重量，组织学分析证实细胞凋亡增加且细胞增殖减少。这些发现强调了FA-Dex-聚（硫化丙烯）-阿霉素在为前列腺癌提供靶向、ROS响应性治疗策略方面的潜在前景。
