【摘 要】
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In order to overcome the limitation of traditional active nano-therapeutic drugs on tumor targeting effciency 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-d
【机 构】
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College of Chemistry,Chemical Engineering and Materials Science,State and Local Joint Engineering La
论文部分内容阅读
In order to overcome the limitation of traditional active nano-therapeutic drugs on tumor targeting effciency 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.
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