Qin Li, Tu Jianfei, Zhao Jiawei, Zhang Yuanke, Li Tiancheng, Zhang Yuqi, Zhang Peng, Ling Guixia, Ji Jiansong
Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
College of Medical Devices, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Colloids Surf B Biointerfaces. 2025 Feb;246:114371. doi: 10.1016/j.colsurfb.2024.114371. Epub 2024 Nov 8.
Conventional chemotherapy drugs are difficult to effectively target tumor tissue, leading to poor treatment outcomes and side effects. Actively targeted and stimuli-responsive nanomedicine greatly improves this situation, allowing for more precise drug accumulation at tumor sites. Herein, carboxymethyl-β-cyclodextrin (CMCD) - based host-guest nanocomposites (NPs) encapsulating hydroxycamptothecin (HCPT) were fabricated, which responded to esterase and had the function of targeting CD 44 receptors and the nucleus. PS-CMCD was firstly synthesized through an amide reaction of protamine (PS) and CMCD to enhance the function of penetrating membrane and nuclear localization. PS-CMCD/HCPT/HA NPs were then prepared by the host-guest complexation of PS-CMCD and HCPT and followed by surface modification of hyaluronic acid (HA) with CD44 receptor-targeting properties. The successful inclusion was also validated through computer simulation. The obtained nanocomposites displayed the esterase-responsive release behaviors of HCPT. Moreover, the synthesized PS-CMCD/HCPT/HA NPs enhanced the intracellular drug uptake due to the tumor cell- and nuclear-mediated targeting. In addition, in vivo application exhibited that PS-CMCD/HCPT/HA NPs realized good antitumor effects. These findings suggested its potential for targeted delivery and more effective tumor therapy.
传统化疗药物难以有效靶向肿瘤组织，导致治疗效果不佳且伴有副作用。主动靶向和刺激响应型纳米药物极大地改善了这种情况，使药物能更精准地在肿瘤部位蓄积。在此，制备了包载羟基喜树碱（HCPT）的基于羧甲基-β-环糊精（CMCD）的主客体纳米复合材料（NPs），其对酯酶有响应，且具有靶向CD44受体和细胞核的功能。首先通过鱼精蛋白（PS）与CMCD的酰胺反应合成PS-CMCD，以增强穿膜和核定位功能。然后通过PS-CMCD与HCPT的主客体络合，随后用具有CD44受体靶向特性的透明质酸（HA）进行表面修饰，制备了PS-CMCD/HCPT/HA NPs。通过计算机模拟也验证了成功包载。所获得的纳米复合材料表现出HCPT的酯酶响应释放行为。此外，合成的PS-CMCD/HCPT/HA NPs由于肿瘤细胞和细胞核介导的靶向作用增强了细胞内药物摄取。另外，体内应用表明PS-CMCD/HCPT/HA NPs实现了良好的抗肿瘤效果。这些发现表明其在靶向递送和更有效的肿瘤治疗方面具有潜力。
