A Trojan horse biomimetic delivery system using mesenchymal stem cells for HIF-1α siRNA-loaded nanoparticles on retinal pigment epithelial cells under hypoxia environment

作     者：Lei Zhang Jie-Jing Yan Hai-Yan Wang Mu-Qiong Li Xi-Xi Wang Li Fan Yu-Sheng Wang 

作者机构：Shaanxi Eye HospitalXi'an People's Hospital(Xi'an Fourth Hospital)Xi'an 710004Shaanxi ProvinceChina Department of OphthalmologyXijing HospitalXi'an 710032Shaanxi ProvinceChina Ophthalmology DepartmentXi'an No.1 Hospitalthe First Affiliated Hospital of Northwest UniversityXi'an 710002Shaanxi ProvinceChina Department of Pharmaceutical Chemistry and Analysis School of Pharmacy Air Force Medical UniversityXi'an 710032Shaanxi ProvinceChina Department of Mathematics and StatisticsUniversity of Arkansas at Little RockLittle RockAR 72204USA 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2022年第15卷第11期

页      面：1743-1751页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：Supported by Key Research and Development Program of Shaanxi Province China (No.2020SF-267) the Natural Science Basis Research Plan in Shaanxi Province of China (No.2022JM-514) Bethune·Lumitin Research Funding for the Young and Middle-aged Ophthalmologists (No.BJ-LM2021011J) Xi’an Science and Technology Project [No.20YXYJ0008(3)] Research Incubation Fund of Xi’an People’s Hospital (Xi’an Fourth Hospital)(No.ZD-5, ZD-7, and ZD-8) 

主　　题：hypoxia mesenchymal stem cells poly(lactic-co-glycolic acid)nanoparticles hypoxia-inducible factor-1α retinal pigment epithelial cells 

摘      要：AIM: To demonstrate the feasibility of mesenchymal stem cell(MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse-like transport of hypoxiainducible factor-1α small interfering RNA(HIF-1α si RNA) between MSCs and retinal pigment epithelial cells(RPE) under hypoxia ***: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed. HIF-1α si RNA was encapsulated into poly(lactic-co-glycolic acid) nanoparticles(PLGA-NPs) through the water-in-oil-in-water(w/o/w) multiple emulsion technique. The effect of PLGANPs uptake on the expression of HIF-1α m RNA was tested in RPE cells by real-time quantitative polymerase chain reaction(q PCR) and additional transfected conditions were used as control, including lentivirus group, nude plasmid group and blank PLGA group. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Transwell co-culture system of transfected MSCs and RPE cells was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α si RNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect of transfected MSCs on HIF-1α expression of RPE cells was analyzed by using q PCR at the time points 24h, 3d, and ***: The average diameter of PLGA-NPs loaded with HIF si RNA was 314.1 nm and the zeta potential was-0.36 m V. The transfection efficiency of PLGA-NPs was 67.3%±5.2% into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α si RNA can effectively reduce the expression of HIF-1α m RNA up to 7d in RPE(0.63±0.05 at 7d, P0.001). In the Transwell co-culture system of transfected MSCs and RPE, the abilities of proliferation(2.34±0.17, 2.40±0.28, 2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83%±2.43%, 12.94%±2.19%, 12.39%±3.21%;F=0.70, P=0.53) and migration(124.5±7.78, 119.5±5.32, 130±9.89, F=1.33, P=0.33) of the RPE cells had no differences between MSClo