Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang 421001, China.
Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System (2018TP1044), School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua 418000, China; College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410000, China.
J Colloid Interface Sci. 2023 Sep 15;646:118-128. doi: 10.1016/j.jcis.2023.05.018. Epub 2023 May 9.
Construction of dual gatekeepers-functionalized mesoporous organic silica nanoparticles (MONs) with both physical and chemical mechanisms for modulated drug delivery properties provides one solution to the extracellular stability vs. intracellular high therapeutic efficiency of MONs that hold great potential for clinical translations.
We reported herein facile construction of diselenium-bridged MONs decorated with dual gatekeepers, i.e., azobenzene (Azo)/polydopamine (PDA) for both physical and chemical modulated drug delivery properties. Specifically, Azo can act as a physical barrier to block DOX in the mesoporous structure of MONs for extracellular safe encapsulation. The PDA outer corona serves not only as a chemical barrier with acidic pH-modulated permeability for double insurance of minimized DOX leakage in the extracellular blood circulation but also for inducing a PTT effect for synergistic PTT and chemotherapy of breast cancer.
An optimized formulation, DOX@(MONs-Azo3)@PDA resulted in approximately 1.5 and 2.4 fold lower IC50 values than DOX@(MONs-Azo3) and (MONs-Azo3)@PDA controls in MCF-7 cells, respectively, and further mediated complete tumor eradication in 4T1 tumor-bearing BALB/c mice with insignificant systematic toxicity due to the synergistic PTT and chemotherapy with enhanced therapeutic efficiency.
构建具有物理和化学双重机制的双门控功能化介孔有机硅纳米粒子（MONs），用于调节药物输送性能，为 MONs 的细胞外稳定性与细胞内高治疗效率提供了一种解决方案，这对于临床转化具有巨大潜力。
我们在此报告了一种简便的方法，用于构建带有双门控剂（即偶氮苯（Azo）/聚多巴胺（PDA））的双硒桥联 MONs，以调节物理和化学药物输送性能。具体而言，Azo 可以作为物理屏障，将 DOX 阻挡在 MONs 的介孔结构中，以实现细胞外安全封装。PDA 外层冠不仅可以作为化学屏障，在细胞外血液循环中具有酸性 pH 调节渗透性，以双重保险最小化 DOX 泄漏，还可以诱导 PTT 效应，用于协同乳腺癌的 PTT 和化疗。
优化后的配方 DOX@(MONs-Azo3)@PDA 在 MCF-7 细胞中的 IC50 值分别比 DOX@(MONs-Azo3)和 (MONs-Azo3)@PDA 对照组低约 1.5 倍和 2.4 倍，并且由于协同的 PTT 和化疗增强了治疗效果，在 4T1 荷瘤 BALB/c 小鼠中进一步实现了完全肿瘤消除，而系统毒性可忽略不计。
