Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Carbohydr Polym. 2015 Aug 1;126:231-9. doi: 10.1016/j.carbpol.2015.03.019. Epub 2015 Mar 18.
Herein, we developed dualfunctional hyaluronic acid (HA)-grafted polyamidoamine (PAMAM) dendrimers for simultaneous systemic long circulation and active tumor targeting and delivery of topotecan hydrochloride (TPT). The possibility of these modified dendrimers as nanocarriers for promoting tissue distribution and antitumor efficiency, as well as a drug release profile, cytotoxicity and cellular uptake, was investigated. The fine targeting efficiency of HA-PAMAM/TPT was confirmed by the CD44 receptor-mediated high cellular uptake efficiency and low cytotoxicity in HCT-116 cells, and the in vivo higher tumor distribution percentage than in other tissues in mice bearing an S-180 tumor. Pharmacokinetic studies showed that the t1/2 and MRT of TPT were significantly extended after intravenous administration of HA-PAMAM/TPT in normal rats. Moreover, TPT-loaded nanovehicles demonstrated higher antitumor activity compared with free drug and PAMAM/TPT. Overall, HA-PAMAM may be an alternative vector for the effective targeted delivery of and tumor therapy with antitumor drugs.
在此，我们开发了具有双重功能的透明质酸（HA）接枝聚酰胺-胺（PAMAM）树枝状大分子，用于同时进行系统的长循环以及喜树碱盐酸盐（TPT）的主动肿瘤靶向和递药。研究了这些修饰的树枝状大分子作为促进组织分布和抗肿瘤效率以及药物释放特性、细胞毒性和细胞摄取的纳米载体的可能性。通过 CD44 受体介导的高细胞摄取效率和低 HCT-116 细胞毒性证实了 HA-PAMAM/TPT 的精细靶向效率，并且在携带 S-180 肿瘤的小鼠中，HA-PAMAM/TPT 在肿瘤中的分布百分比高于其他组织。药代动力学研究表明，HA-PAMAM/TPT 静脉给药后，TPT 的 t1/2 和 MRT 显著延长。此外，载药纳米载体与游离药物和 PAMAM/TPT 相比，表现出更高的抗肿瘤活性。总的来说，HA-PAMAM 可能是用于有效靶向递药和肿瘤治疗的抗肿瘤药物的替代载体。
