Monoclonal Antibody-conjugated Polyphosphoester- hyd -DOX Prodrug Nanoparticles for Targeted Chemotherapy of Liver Cancer Cells
2021
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.
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