Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, Zhejiang 313000, China; Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L3G1, Canada; School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, Jiangxi 332000, China.
School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, Jiangxi 332000, China.
Biomed Pharmacother. 2024 May;174:116446. doi: 10.1016/j.biopha.2024.116446. Epub 2024 Mar 20.
Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.
在这里，我们构建了创新的还原敏感和靶向明胶基胶束，用于肿瘤治疗中的阿霉素（DOX）递送。合成并表征了 AS1411 适配体修饰的明胶-ss-生育酚琥珀酸酯（AGSST）和没有 AS1411 修饰的对照 GSST。制备了含有抗肿瘤药物 DOX 的 AGSST（AGSST-D）和 GSST-D 纳米粒，其形状几乎为球形。体外 DOX 释放的还原响应特性在 AGSST-D 和 GSST-D 中得到揭示。与非靶向 GSST-D 相比，AGSST-D 对核仁素过表达的 A549 细胞表现出更好的细胞内摄取和更强的细胞毒性。重要的是，AGSST-D 胶束在荷瘤小鼠中的杀伤活性比 GSST-D 和 DOX·HCl 更有效。结果表明，AGSST-D 胶束没有明显的全身毒性。总的来说，AGSST 胶束有可能成为靶向肿瘤治疗的有效药物载体。
