Abstract：
The recent challenge in enhancing the targeted delivery of anticancer drugs to cancer cells is improving the bioavailability and therapeutic efficacy of drug delivery systems while minimizing their systemic side effects. In this study, the MIL-88(Fe) metal-organic framework was synthesized using the in situ method in the presence of hydroxyapatite nanoparticles (HAP) toward the HAP/MIL-88(Fe) (HM) nanocomposite preparation. It was then functionalized with mannose (M) as an anticancer receptor through the Steglich esterification method. Various analyses confirmed the successful synthesis of MHM. For drug release investigation, 5-Fu was loaded into the MHM, which was then coated with a hyaluronic acid (HA) hydrogel film. Characterization analyses verified the structure of the resulting HA/5-Fu-MHM hydrogel film. In vitro drug release experiments showed that the release of 5-Fu drug from HA/5-Fu-MHM could be controlled with pH, reducing its release rate in the acidic environment of the stomach while increasing it in the intestinal environment. Cytotoxicity results of the HA/5-Fu-MHM hydrogel film against HT29 cancer cells showed enhanced cytotoxicity due to the mannose and hyaluronic acid in its structure, which triggers a dual-targeted drug delivery system. The obtained results indicate that the prepared hydrogel films can be a promising bio-platform for colon cancer treatment.
摘要：
增强抗癌药物向癌细胞的靶向递送的最近挑战是提高药物递送系统的生物利用度和治疗功效,同时使其全身副作用最小化。在这项研究中,在羟基磷灰石纳米颗粒（HAP）存在下，使用原位方法合成了MIL-88（Fe）金属-有机骨架，以制备HAP/MIL-88（Fe）（HM）纳米复合材料。然后通过Steglich酯化方法用甘露糖(M)作为抗癌受体进行官能化。各种分析证实了MHM的成功合成。对于药物释放调查，5-Fu被装载到MHM中，然后用透明质酸(HA)水凝胶膜涂覆。表征分析证实了所得HA/5-Fu-MHM水凝胶膜的结构。体外释药实验表明,5-Fu药物在HA/5-Fu-MHM中的释放受pH控制,降低其在胃的酸性环境中的释放速率，同时增加其在肠道环境中的释放速率。HA/5-Fu-MHM水凝胶膜对HT29癌细胞的细胞毒性结果表明，由于其结构中的甘露糖和透明质酸，细胞毒性增强。这触发了双靶向药物递送系统。所获得的结果表明,所制备的水凝胶膜可以是用于结肠癌治疗的有希望的生物平台。
