CRGDK-Functionalized PAMAM-Based Drug-Delivery System with High Permeability
CRGDK-Functionalized PAMAM-Based Drug-Delivery System with High Permeability
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DOI：
10.1021/acsomega.0c00202
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发表时间：
2020-04-28
期刊：
影响因子：
4.1
通讯作者：
Teng, Gaojun
中科院分区：
文献类型：
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作者：
Liu, Dongfang;Wang, Chao;Teng, Gaojun
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。减小纳米药物的尺寸或整合穿透肽已被证明非常有助于提高纳米药物的肿瘤渗透性。本文设计了一种以穿透肽CRGDK功能化的聚酰胺-胺（PAMAM）作为药物载体，其直径约为5 nm。紫杉醇（PTX）被用作模型药物，并通过生物可裂解的酯键共价连接到载体。CRGDK功能化的载药纳米颗粒比其非靶向对应物表现出更高的细胞摄取和更高的肿瘤蓄积和渗透，这也赋予功能化纳米药物比其非靶向对应物和临床紫杉醇制剂更高的抗肿瘤效率。基于PAMAM的肽基纳米药物的良好性能表明，我们的策略是可行的，以提高肿瘤的积累和渗透的纳米药物。
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 similar to 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.