Liu Yehong, Chen Miaoxin, Li Gaoyang, Xu Shouhong, Liu Honglai
State Key Laboratory of Chemical Engineering and School of Chemistry & Molecular Engineering, East China University of Science and Technology Shanghai 200237 P.R. China
RSC Adv. 2022 Jun 29;12(30):19063-19071. doi: 10.1039/d2ra02290g.
In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HAgel and MSN-HAgel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of "1 + 1 > 2", providing a novel idea for cancer treatments.
在本研究中，设计了一种基于介孔二氧化硅纳米颗粒（MSNs）的含42nt核酸适配体（HApt）的pH/还原双重响应载体。使用两种低分子量寡聚透明质酸（HA）接枝到MSN上以实现更好的药物包封。通过对HA侧链上的羧基进行巯基化反应交联HA链，制备了交联的MSN-HAgel和MSN-HAgel。在交联反应过程中加入适量的巯基核酸（HApt-SH），实现了对过表达HER2受体的癌细胞的靶向能力和凋亡功能。交联的HA对降低阿霉素的副作用效果良好，在正常体内环境下药物泄漏率小于20%。然而，它能在肿瘤环境中实现快速高效的药物释放。至于HApt的释放，它对谷胱甘肽（GSH）表现出良好的响应。细胞毒性试验表明，HAgel中含有的HApt对SKBR3细胞具有很大的靶向作用和显著的细胞毒性。总体而言，这种MSN-HAgel实现了基因治疗和化疗的结合，展现出“1 + 1 > 2”的协同效应，为癌症治疗提供了新思路。
