a.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
b.Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, China
phni@suda.edu.cn
收稿:2021-02-25,
修回:2021-3-13,
录用:2021-3-19,
网络首发:2021-06-25,
纸质出版:2021-09-18
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Huang, Y. K.; Tian, H. R.; Zhang, M. Z.; He, J. L.; Liu, J.; Ni, P. H. Monoclonal antibody-conjugated polyphosphoester-hyd-DOX prodrug nanoparticles for targeted chemotherapy of liver cancer cells. Chinese J. Polym. Sci. 2021, 39, 1392–1402
Ya-Kui Huang, Hong-Rui Tian, Ming-Zu Zhang, et al. Monoclonal Antibody-conjugated Polyphosphoester-
Huang, Y. K.; Tian, H. R.; Zhang, M. Z.; He, J. L.; Liu, J.; Ni, P. H. Monoclonal antibody-conjugated polyphosphoester-hyd-DOX prodrug nanoparticles for targeted chemotherapy of liver cancer cells. Chinese J. Polym. Sci. 2021, 39, 1392–1402 DOI: 10.1007/s10118-021-2582-3.
Ya-Kui Huang, Hong-Rui Tian, Ming-Zu Zhang, et al. Monoclonal Antibody-conjugated Polyphosphoester-
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 H
2
N-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 (IC
50
: 1.12 mg·L
−1
) against HepG2 cells than PDNPs (IC
50
: 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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