具有高渗透性的CRGDK功能化聚酰胺-胺型药物递送系统
CRGDK-Functionalized PAMAM-Based Drug-Delivery System with High Permeability.
作者信息
Liu Dongfang, Wang Chao, Yang Jian, An Yanli, Yang Rui, Teng Gaojun
机构信息
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, No. 87, Dingjiaqiao, Nanjing 210009, China.
Central Laboratory, Wuxi Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, Jiangsu Province, China.
出版信息
ACS Omega. 2020 Apr 14;5(16):9316-9323. doi: 10.1021/acsomega.0c00202. eCollection 2020 Apr 28.
The low tumor permeability of nanomedicines is a major challenge for their application in tumor therapy. Reducing the size of nanomedicines or integrating penetrating peptides has been demonstrated to be very helpful to improve the tumor permeability of nanomedicines. In this paper, poly(amidoamine) (PAMAM) functionalized with the penetrating peptide CRGDK was designed as a drug carrier with a diameter of ∼5 nm. Paclitaxel (PTX) was used as a model drug and covalently linked to the carrier via a biocleavable ester bond. The CRGDK-functionalized drug-loaded nanoparticle exhibited a higher cellular uptake and a higher tumor accumulation and penetration than its nontargeted counterpart, which also endowed the functionalized nanomedicine with a higher antitumor efficiency than its nontargeted counterpart and the clinical Taxol formulation. The good performance of the peptide-bearing PAMAM-based nanomedicine indicates that our strategy is feasible to improve the tumor accumulation and penetration of nanomedicines.
纳米药物的低肿瘤渗透性是其在肿瘤治疗中应用的主要挑战。已证明减小纳米药物的尺寸或整合穿透肽有助于提高纳米药物的肿瘤渗透性。本文设计了用穿透肽CRGDK功能化的聚（酰胺胺）（PAMAM）作为直径约为5nm的药物载体。紫杉醇（PTX）用作模型药物，并通过可生物裂解的酯键与载体共价连接。与未靶向的对应物相比，CRGDK功能化的载药纳米颗粒表现出更高 的细胞摄取、更高的肿瘤积累和穿透能力，这也赋予了功能化纳米药物比未靶向的对应物和临床紫杉醇制剂更高的抗肿瘤效率。含肽的基于PAMAM的纳米药物的良好性能表明我们的策略对于提高纳米药物的肿瘤积累和穿透能力是可行的。
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