D-T7 Peptide Modified PEGylated Bilirubin Nanoparticles Loaded with Cediranib and Paclitaxel for Antiangiogenesis and Chemotherapy of Glioma
D-T7 Peptide Modified PEGylated Bilirubin Nanoparticles Loaded with Cediranib and Paclitaxel for Antiangiogenesis and Chemotherapy of Glioma
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负载西地尼布和紫杉醇的 D-T7 肽修饰聚乙二醇化胆红素纳米粒用于胶质瘤的抗血管生成和化疗
DOI：
10.1021/acsami.8b16219
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发表时间：
2019
影响因子：
9.5
通讯作者：
Huile Gao
中科院分区：
文献类型：
--
作者：
Meinan Yu;Dunyan Su;Yuanyuan Yang;Lin Qin;Chuan Hu;Rui Liu;Yang Zhou;Chuanyao Yang;Xiaotong Yang;Guanlin Wang;Huile Gao
血脑肿瘤屏障（BTB）和血脑屏障（BBB）一直是胶质瘤治疗的主要屏障。本研究提出了D-T7肽修饰纳米粒主动靶向胶质瘤，通过克服血脑屏障和脑屏障来提高抗胶质瘤的疗效。胶质瘤靶向实验表明，D-T7肽修饰的纳米颗粒的渗透效果比未修饰的纳米颗粒高7.89倍。西地尼布（CD）和紫杉醇（PTX）联合应用于抗血管生成和化疗治疗脑胶质瘤。聚乙二醇化胆红素纳米粒（BRNPs）由于具有抗氧化、抗炎和活性氧响应能力而被选择作为合适的药物递送系统（CD&PTX@TBRBPs）。MTT法和细胞凋亡实验结果显示，CD &PTX@ TBRNP组细胞毒性最强，中位生存时间分别是生理盐水组和CD & PTX @ BRNP组的3.31倍和1.23倍。以上结果表明，我们构建了一种新型的肽修饰的双重药物载体，具有更强的抗胶质瘤作用。
The blood–brain tumor barrier (BTB) and blood–brain barrier (BBB) have always been the major barriers in glioma therapy. In this report, we proposed D-T7 peptide-modified nanoparticles actively targeted glioma by overcoming the BBB and BTB to improve the antiglioma efficacy. Glioma-targeting experiments showed that the penetration effect of the D-T7 peptide-modified nanoparticles was 7.89-fold higher than that of unmodified nanoparticles. Furthermore, cediranib (CD) and paclitaxel (PTX) were used for the combination of the antiangiogenesis and chemotherapy for glioma. PEGylated bilirubin nanoparticles (BRNPs) were selected as a suitable drug delivery system (CD&PTX@TBRBPs) owing to the antioxidant, anti-inflammatory, and reactive oxygen species-responsive ability. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays showed that CD&PTX@TBRBPs had the highest cytotoxicity and the median survival time of the CD&PTX@TBRNP group was 3.31-fold and 1.23-fold longer than that of the saline and CD&PTX@BRNP groups, respectively. All the results showed that we constructed a novel and accessible peptide-modified dual drug carrier with an enhanced antiglioma effect.