Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, P. R. China.
Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1499-1507. doi: 10.1021/acsabm.0c01388. Epub 2021 Feb 2.
A tumor-penetrating peptide, iRGD (a tumor-homing peptide, CRGDKGPDC), could enhance the penetration of drugs via the specific receptor-binding affinity to αvβ3 and NRP-1 that overexpressed on tumor vasculature and tumor cells. Considering the side effects of traditional chemotherapy, here, poly(ethylene glycol) (PEG, Mw = 7500)-based and iRGD-modified poly(ethylene glycol)-based nanoparticles were successfully prepared. iRGD, as a tumor-targeting and tumor-penetrating agent, was combined with PEG after the esterification reaction between PEG and diosgenin (DGN). After the efficient loading of 10-hydroxycamptothecin (HCPT), the iRGD-PEG-DGN/HCPT NPs of chemotherapy were established. The characteristics of iRGD-PEG-DGN/HCPT NPs were evaluated. This nano-delivery system possessed high drug loading efficiency (∼17.34 wt % HCPT), controlled release rate, good pH response, and iRGD active targeting and passive targeting with an appropriate size (∼140 nm). All these features forcefully indicated that the iRGD-modified drug delivery system could markedly ameliorate the tumor therapy efficacy compared to the nontargeted nanoparticles through enhancing the tumor accumulation and penetration.
一种肿瘤穿透肽，iRGD（一种肿瘤归巢肽，CRGDKGPDC），可以通过与肿瘤血管和肿瘤细胞上过度表达的αvβ3 和 NRP-1 的特异性受体结合亲和力增强药物的穿透。考虑到传统化疗的副作用，这里成功制备了基于聚乙二醇（PEG，Mw=7500）和 iRGD 修饰的聚乙二醇纳米粒子。iRGD 作为一种肿瘤靶向和肿瘤穿透剂，在 PEG 与薯蓣皂素（DGN）之间的酯化反应后与 PEG 结合。在 10-羟基喜树碱（HCPT）的高效负载后，建立了化疗用 iRGD-PEG-DGN/HCPT NPs。对 iRGD-PEG-DGN/HCPT NPs 的特性进行了评估。这种纳米递药系统具有高载药效率（17.34wt%HCPT）、控释率、良好的 pH 响应性以及适当大小（140nm）的 iRGD 主动靶向和被动靶向。所有这些特征都有力地表明，与非靶向纳米颗粒相比，通过增强肿瘤积累和穿透，iRGD 修饰的药物递送系统可以显著改善肿瘤治疗效果。
