Preparation and characterization of enzyme-responsive zwitterionic nanoparticles for monoclonal antibody delivery

Abstract

Monoclonal antibodies have been used in many diseases, but how to improve their delivery efficiency is still a key issue. As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies, in this study, zwitterionic monomers, sulfobetaine methacrylate (SBMA), and 3-[[2-(methacryloyloxy) ethyl] dimethylammonio] propionate (CBMA) were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions. The results from dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent. These nanoparticles were spherical with the sizes of (18.7±1.9) nm (SBMA nanoparticle) and (18.2±2.1) nm (CBMA nanoparticle), and the surface contained zwitterionic polymers. It was revealed that they had no cytotoxicity, could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells, and was able to effectively penetrate endothelial cells (> 2%) by transwell. Therefore, the development of this strategy has a great prospect for the delivery of monoclonal antibodies.

Graphical abstract

Keywords

zwitterionic polymer / monoclonal antibody delivery / enzyme responsive release / penetration of endothelial cell

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