Monoclonal Antibody-conjugated Polyphosphoester-hyd-DOX Prodrug Nanoparticles for Targeted Chemotherapy of Liver Cancer Cells  

作　　者：Ya-Kui Huang Hong-Rui Tian Ming-Zu Zhang Jin-Lin He Jian Liu Pei-Hong Ni 

机构地区：[1]College of Chemistry,Chemical Engineering and Materials Science,State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials,Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis,Soochow University,Suzhou 215123,China [2]Institute of Functional Nano and Soft Materials(FUNSOM),Soochow University,Suzhou 215123,China

出　　处：《Chinese Journal of Polymer Science》2021年第11期1392-1402,共11页高分子科学（英文版）

基　　金：financial supports from the National Natural Science Foundation of China(Nos.21975169 and 21374066);the Natural Science Foundation of Jiangsu Province(No.BK20171212);Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions。

摘　　要：In order to overcome the limitation of traditional active nano-therapeutic drugs on tumor targeting efficiency which cannot reach the receptor/target in sufficient amount in the body,in this work,we developed a monoclonal antibody(mAb)and a polymer-hyd-doxorubicin prodrug conjugate,which enables the self-assembled nanoparticles to have precise targeting,tumor tissue aggregation and pH-sensitive drug release.We first prepared an amphiphilic polymer prodrug,abbreviated as H2N-PEEP-b-PBYP-hyd-DOX,via a combination of ring-opening polymerization(ROP)and"click"chemistry,in which PEEP and PBYP represent two kinds of phosphoester segmemts,-hyd-is hydrazone bond.After self-assembly into prodrug nanoparticles(PDNPs)with a diameter of about 93 nm,CD147 mAb was conjugated onto the PDNPs by EDC/NHS chemistry to form mAb-PDNPs.For the PDNPs and mAb-PDNPs,we also investigated their stability,in vitro drug release behavior and cellular uptake.The results showed that the pH-responsive PDNPs can remain relatively stable under the condition of PB 7.4 buffer solution.However,under acidic conditions or in the presence of phosphodiesterase I(PDE I),both the amount and rate of DOX release increased at the same incubation period.Cytotoxicity assay showed that mAb-PDNPs exhibited higher cytotoxicity(IC50:1.12 mg·L^(-1))against HepG2 cells than PDNPs(IC50:2.62 mg·L^(-1))without monoclonal antibody.The nanoparticles with antibodies mAb-PDNPs have relatively better stability and can directly achieve the targeting drug delivery through CD147 mAb.

关 键 词：Monoclonal antibody Polymeric prodrug POLYPHOSPHOESTER Drug delivery Targeted therapy 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程]