Preparation and evaluation of tumour microenvironment response multistage nanoparticles for epirubicin delivery and deep tumour penetration
Preparation and evaluation of tumour microenvironment response multistage nanoparticles for epirubicin delivery and deep tumour penetration
复制标题
用于表阿霉素递送和肿瘤深度渗透的肿瘤微环境响应多级纳米粒子的制备和评估
DOI：
10.1080/21691401.2018.1470528
复制
发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Sun, Yong
中科院分区：
文献类型：
--
作者：
Dai, Jialing;Han, Shangcong;Sun, Yong
Abstract Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI). Due to the protonation of tertiary amine groups of PDPA segment in acid environment, mPEG-PDPA-PG could enhance the lysosomal escape and the intracellular release of EPI. This NPs/HAase/G-iRGD delivery system showed great biocompatibility in vitro, confirmed by MTT method. In vitro spherical tumour model penetration and in vivo tumour permeability investigation showed HAase coated NPs-EPI (NPs-EPI/HAase) could significantly enhance its penetrating efficiency. The NPs-EPI/HAase could assist in breaking down the hyaluronic acid (HA), which was a key component of extracellular matrix and thereby improving mass transport within the solid tumours. The flow cytometry studies showed that G-iRGD coated NPs-EPI (NPs-EPI/G-iRGD) was more easily taken up by HepG2 cells than gelatin coated NPs-EPI (NPs-EPI/G), which revealed the active targeting ability of iRGD. The results proved that this NPs/HAase/G-iRGD delivery system showed promising potential in enhancing tumour penetration efficiency.
