Xu Lei, Wu Shuo, Zhou Xiaoqiu
Department of Internal Medicine, School Hospital of Beihua University, Jilin, China.
J Biomater Appl. 2018 Jul;33(1):72-81. doi: 10.1177/0885328218772721. Epub 2018 Apr 26.
Drug-loaded nanoparticles have been widely researched in the antitumor. However, some of them are unsatisfactory in the long blood circulation and controlled drug release. Red blood cell (RBC) membrane vesicles (RV)-coated nanoparticles have gained more and more attention in drug delivery for their many unique advantages, such as excellent stability, long blood circulation, and reduced the macrophage cells uptake. Herein, by utilizing the advantages of RV, we fabricated RV-coated poly(lactide- co-glycolide) (PLGA)-docetaxel (RV/PLGA/DTX) nanoparticles to enhance the antitumor efficiency in vivo. The RV/PLGA/DTX showed spherical morphology with particle size of about 100 nm and zeta potential at -12.63 mV, which could maintain stability for a long time. The RV/PLGA/DTX significantly enhanced cellular uptake of DTX compared to PLGA/DTX in HepG2 cells. Moreover, RV/PLGA/DTX showed the strongest antitumor effect in vitro. Prolonged blood circulation and enhanced DTX accumulation at the tumor site through enhanced permeability and retention (EPR) effect were achieved by RV/PLGA/DTX, which eventually obtained satisfactory antitumor effect and depressed system toxicity on mice bearing HepG2 xenografts mouse models when compared with free DTX. The hematoxylin and eosin (H&E) and immunofluorescence assays further proved the advantages of RV/PLGA/DTX in vivo antitumor. These RV-coated nanoparticles provide a mimetic therapy, completely inhibited the growth of the HepG2 cells, and with simple compositions, suggesting it to be an ideal strategy for improving the antitumor effect of drug-loaded nanoparticles.
载药纳米颗粒在抗肿瘤领域已得到广泛研究。然而,其中一些在长循环和药物控释方面并不理想。红细胞(RBC)膜囊泡(RV)包被的纳米颗粒因其诸多独特优势,如出色的稳定性、长循环以及减少巨噬细胞摄取等,在药物递送中越来越受到关注。在此,利用RV的优势,我们制备了RV包被的聚(丙交酯-乙交酯)(PLGA)-多西他赛(RV/PLGA/DTX)纳米颗粒,以提高体内抗肿瘤效率。RV/PLGA/DTX呈现球形形态,粒径约为100 nm,zeta电位为-12.63 mV,可长时间保持稳定。与PLGA/DTX相比,RV/PLGA/DTX在HepG2细胞中显著增强了多西他赛的细胞摄取。此外,RV/PLGA/DTX在体外显示出最强的抗肿瘤作用。RV/PLGA/DTX通过增强渗透和滞留(EPR)效应实现了延长血液循环并增强多西他赛在肿瘤部位的蓄积,与游离多西他赛相比,最终在携带HepG2异种移植瘤小鼠模型上获得了满意的抗肿瘤效果并降低了系统毒性。苏木精和伊红(H&E)染色及免疫荧光分析进一步证明了RV/PLGA/DTX在体内抗肿瘤方面的优势。这些RV包被的纳米颗粒提供了一种模拟疗法,完全抑制了HepG2细胞的生长,且组成简单,表明它是提高载药纳米颗粒抗肿瘤效果的理想策略。