Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xian 710127, Shaanxi, China.
School of Materials Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, China.
ACS Appl Mater Interfaces. 2021 Sep 15;13(36):42522-42532. doi: 10.1021/acsami.1c14189. Epub 2021 Aug 31.
Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.
肿瘤靶向递药和抗癌药物的控制释放是提高化疗疗效和降低不良反应的有前途的策略。尽管介孔硅纳米粒子（MSNs）已被认为是阿霉素（DOX）的潜在递送系统，但由于其大的开放孔的不可控泄漏和突释，限制了其应用。在此，我们基于 MSN-药物负载、细胞膜模拟涂层、按需孔阻塞/开放和肿瘤细胞靶向策略，设计了一种智能药物递送系统（智能 MSN-药物）。通过聚多巴胺涂层缩小了载 DOX 的 MSNs 的孔径，并通过肿瘤环境破坏的 -SS- 链锚定的肿瘤靶向配体阻塞了孔/通道。此外，构建了细胞膜模拟表面以增强智能 MSN-药物的生物相容性。共聚焦显微镜结果表明，智能 MSN-药物被 HeLa 细胞高度选择性摄取（与 L929 细胞相比增加 12 倍），并递送到 HeLa 细胞的核内。进一步的体外 IC 研究表明，智能 MSN-药物对 HeLa 细胞的毒性比正常成纤维细胞高 4000 倍。这些令人兴奋的结果表明，智能 MSN-药物具有选择性杀伤肿瘤细胞和保护正常细胞的能力。
