Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles
10.11665/j.issn.1000-5048.20210306
- VernacularTitle:pH响应性PTEN/PLGA-(HE)10-MAP纳米粒的构建及体外评价
- Author:
Qin YONG
1
;
Hanxun YUE
;
Min SHI
;
Shiqin HUANG
;
Xuan ZHAO
;
Xian YU
Author Information
1. 重庆医科大学附属第二医院Ⅰ期临床试验研究室
- Publication Type:Journal Article
- Keywords:
nanoparticle;
pH-responsive;
PLGA;
tumor-targeted;
cell-penetrating peptides;
gene delivery
- From:
Journal of China Pharmaceutical University
2021;52(3):301-310
- CountryChina
- Language:Chinese
-
Abstract:
To construct PTEN/PLGA-(HE)10-MAP nanoparticles, which encapsulated PTEN plasmid DNA and combined with the pH-responsive cell-penetrating peptides (CPPs), and to investigate their effects of gene delivery and anti-tumor targets in vitro. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTEN plasmid DNA were prepared by double emulsification-solvent evaporation method. PTEN/PLGA-(HE)10-MAP nanoparticles were prepared by coupling the histidine-glutamic acid-model amphipathic peptide nanocomplex [(HE)10-MAP] to the surface through amide condensation reaction. Particle size, Zeta potential, encapsulation rate and drug loading were tested to characterize the nanoparticles. By analyzing the cytotoxicity, cellular uptake, targeted transfection of eukaryotic expression plasmids and anti-tumor cell proliferation, the feasibility as a targeted gene delivery system were evaluated. The particle size of PTEN/PLGA-(HE)10-MAP nanoparticles was (266.5 ± 2.86) nm, with the encapsulation efficiency (80.6 ± 6.11)%. Zeta potentials were -(6.7 ± 0.26) mV, +(0.7 ± 0.22) mV and +(37.5 ± 0.85) mV at pH 7.4, 7.0 and 6.5, respectively. In the cytotoxicity test, the cell survival rates of tumor and normal cells were above 80%.Non-loading PLGA-(HE)10-MAP nanoparticles showed no obvious cytotoxicity. The results of cellular uptake experiments showed that PTEN/PLGA-(HE)10-MAP nanoparticles were more readily taken up by cells.The results of CCK-8 showed that the nanoparticles could pH-specifically inhibit proliferation of tumor cell in vitro.And PTEN/PLGA-(HE)10-MAP nanoparticles may be applied in tumor gene therapy.
