Xu Xuemei, Ma Jun, Zeng Weikang, Zhang Shucheng, Kong Yanyan, Liu Teng, Zhang Jiajia
Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Anti-Infective Agent Creation Engineering Research Centre of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu 610106, China.
ACS Omega. 2025 Aug 12;10(33):37353-37365. doi: 10.1021/acsomega.5c02939. eCollection 2025 Aug 26.
Selenium nanoparticles (SeNPs) exhibit tumor-suppressive capabilities via reactive oxygen species (ROS)-mediated mitochondrial dysfunction, yet their biomedical application remains constrained by poor targeting specificity and aqueous instability. Herein, we engineered glutathione-responsive therapeutic nanoparticles by encapsulating SeNPs within mesoporous organosilica (MON) isolation layers to ensure aqueous stability, while conjugating LXL-1 aptamers for targeted delivery to triple-negative MDA-MB-231 breast cancer cells. In vitro assessments across breast cell lines (MDA-MB-231 vs MCF-10A/MCF-7) revealed a 5.32-fold increase in cellular uptake of functionalized SeNPs in target cells, attributed to aptamer-mediated recognition. The optimized nanoformulation exhibited potent cytotoxicity comparable to doxorubicin-loaded MON controls at equivalent doses. Moreover, the aptamer-functionalized system significantly reduced cancer cell survival compared to the unmodified group (IC = 161.2 μg/mL vs 71.13 μg/mL). This dual-functional nanoplatform not only enhances tumor-specific accumulation of SeNPs but also establishes a chemotherapy-alternative strategy with minimized systemic toxicity, advancing the development of selenium-based targeted nanomedicines.
硒纳米颗粒（SeNPs）通过活性氧（ROS）介导的线粒体功能障碍展现出肿瘤抑制能力，但其生物医学应用仍受靶向特异性差和水相不稳定性的限制。在此，我们通过将SeNPs封装在介孔有机硅（MON）隔离层中来构建谷胱甘肽响应性治疗性纳米颗粒，以确保水相稳定性，同时偶联LXL-1适配体，用于靶向递送至三阴性MDA-MB-231乳腺癌细胞。对乳腺癌细胞系（MDA-MB-231与MCF-10A/MCF-7）进行的体外评估显示，靶细胞中功能化SeNPs的细胞摄取增加了5.32倍，这归因于适配体介导的识别。优化后的纳米制剂在等效剂量下表现出与载有阿霉素的MON对照相当的强细胞毒性。此外，与未修饰组相比，适配体功能化系统显著降低了癌细胞存活率（IC = 161.2 μg/mL对71.13 μg/mL）。这种双功能纳米平台不仅增强了SeNPs在肿瘤中的特异性积累，还建立了一种全身毒性最小的化疗替代策略，推动了基于硒的靶向纳米药物的发展。
