Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China.
Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin, 150001, PR China; College of Sciences, Heihe University, Heihe, 164300, PR China.
Biomaterials. 2019 Dec;223:119473. doi: 10.1016/j.biomaterials.2019.119473. Epub 2019 Sep 3.
Drug delivery systems (DDSs) have emerged to help delivering the required cargo into the region of the tumor, achieving the objectives of extenuating the potential damage to the body and improving the therapeutic effectiveness. Here, we developed a one-pot process for encapsulating the unstable and hydrophobic d-α-Tocopherol succinate (α-TOS) in zeolitic imidazolate framework-8 (ZIF-8) compounds (defined as α-TOS@ZIF-8) and subsequently coated with a hyaluronic acid (HA) shell to form the HA/α-TOS@ZIF-8 nanoplatform. Of particular note was when the concentration of α-TOS is l mg/mL, the loading rate was high up to 43.03 wt%. The study verified that HA shell, which could act as a smart "switch" and tumor-targeted "guider", had the capacity for extending blood circulation, enhancing the tumor-specific accumulation of DDS via CD44-mediated pathway. HA shell could be disintegrated by hyaluronidase (HAase) in the tumor microenvironment (TME) and the wrapped α-TOS@ZIF-8 exposed, thus leading to the decomposition of ZIF-8 in tumor acidic microenvironment to release the loaded α-TOS. Therefore, the HA/α-TOS@ZIF-8 nanoplatform has been achieved as a tumor-specific and on-demand drug delivery system, which improved the treatment efficiency.
药物传递系统（DDS）的出现有助于将所需的药物有效递送到肿瘤区域，实现减轻对身体的潜在损害和提高治疗效果的目标。在这里，我们开发了一种将不稳定且疏水性的 d-α-生育酚琥珀酸酯（α-TOS）封装在沸石咪唑酯骨架-8（ZIF-8）化合物中的一锅法工艺（定义为α-TOS@ZIF-8），并随后用透明质酸（HA）壳进行包覆，形成 HA/α-TOS@ZIF-8 纳米平台。值得注意的是，当α-TOS 的浓度为 1mg/mL 时，载药率高达 43.03wt%。研究证实，HA 壳可以作为一种智能“开关”和肿瘤靶向“引导器”，通过 CD44 介导的途径延长血液循环，增强 DDS 的肿瘤特异性积累。HA 壳可以在肿瘤微环境（TME）中的透明质酸酶（HAase）作用下分解，暴露出包裹的α-TOS@ZIF-8，从而导致在肿瘤酸性微环境中 ZIF-8 的分解，释放出负载的α-TOS。因此，HA/α-TOS@ZIF-8 纳米平台已成为一种肿瘤特异性和按需药物传递系统，提高了治疗效率。
