文献类型：期刊文献

中文题名：Preparation and purification of novel phosphatidyl prodrug and performance modulation of phosphatidyl nanoprodrug

作者：Rui Niu[1];PeiLei Zhang[1];Feng-Qing Wang[1];Min Liu[1];QingHai Liu[1];Ning Jia[1];ShengLi Yang[1];XinYi Tao[1];DongZhi Wei[1]

机构：[1]State Key Laboratory of Bioreactor Engineering,Newworld Institute of Biotechnology,East China University of Science and Technology,Shanghai,200237,China

年份：2019

卷号：6

期号：1

起止页码：120

中文期刊名：Bioresources and Bioprocessing

外文期刊名：生物资源与生物加工(英文)

基金：financially supported by the National Natural Science Foundation of China(Grant No.81603056);by the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

语种：英文

中文关键词：Phosphatidyl prodrug;Purification;Gradient elution;Silica gel column chromatography;PEGylation;RGD modification

摘要：Background A novel phosphatidyl nanoprodrug system can be selectively released parent drugs in cancer cells,triggered by the local overexpression of phospholipase D(PLD).This system significantly reduces the intrinsic disadvantages of conventional chemotherapeutic drugs.However,the separation and purification processes of phosphatidyl prodrug,the precursor of phosphatidyl nanoprodrug,have not been established,and the preparation of nanocrystals with good stability and tumor-targeting capability is still challenging.Results In this study,we established a successive elution procedure for the phosphatidyl prodrug—phosphatidyl mitoxantrone(PMA),using an initial ten-bed volume of chloroform/methanol/glacial acetic acid/water(26/10/0.8/0.7)(v/v/v/v)followed by a five-bed volume(26/10/0.8/3),with which purity rates of 96.93%and overall yields of 50.35%of PMA were obtained.Moreover,to reduce the intrinsic disadvantages of conventional chemotherapeutic drugs,phosphatidyl nanoprodrug—PMA nanoprodrug(NP@PMA)—was prepared.To enhance their stability,nanoparticles were modified with polyethylene glycol(PEG).We found that nanoprodrugs modified by PEG(NP@PEG-PMA)were stably present in RPMI-1640 medium containing 10%FBS,compared with unmodified nanoprodrug(NP@PMA).To enhance active tumor-targeting efficiency,we modified nanoparticles with an arginine-glycine-aspartic acid(RGD)peptide(NP@RGD-PEG-PMA).In vitro cytotoxicity assays showed that,compared with the cytotoxicity of NP@PEG-PMA against tumor cells,that of NP@RGD-PEG-PMA was enhanced.Thus,RGD modification may serve to enhance the active tumor-targeting efficiency of a nanoprodrug,thereby increasing its cytotoxicity.Conclusions A process for the preparation and purification of novel phosphatidyl prodrugs was successfully established,and the nanoprodrug was modified using PEG for enhanced nanoparticle stability,and using RGD peptide for enhanced active tumor-targeting efficiency.These procedures offer considerable potential in the development of functional antitumor prodrugs.