Integrin receptor mediated pH-responsive nano-hydrogel based on histidine-modified poly(aminoethyl methacrylamide) as targeted cisplatin delivery system

Abstract

Abstract The aim of this project was to synthesize a novel nano-hydrogel (NH) and application of this nanomaterial to targeted delivery of cisplatin. The nano-hydrogel (NH) based on random copolymerization of aminoethyl methacrylamide cross-linked with polyethylene glycol dimethacrylate, was fabricated by reversible addition-fragmentation chain transfer method. l -histidine was conjugated to the backbone of the prepared structure. Then, the complexation of cisplatin with NHs was accomplished and tetraiodothyroacetic acid was conjugated to this structure. The NH structure was characterized by FT-IR and 1H NMR analyses. Particle sizes, ζ-potential, molecular weight, and morphology of NHs were determined. The concentrations of cisplatin during drug loading and release studies were quantified using ICP-OES. The cytotoxicity of NHs was evaluated by the MTT assay in HEK293 and HT29\xa0cell lines. Finally, the plasma profiles of the developed NHs were evaluated in Sprague Dawley rats and pharmacokinetic parameters were calculated. The proposed nano-platform is capable of responding to pH changes in the tumor microenvironment and can actively target the cancerous cells more efficiently than free cisplatin in HT29\xa0cells and potentially can serve as an anti-cancer agent. Also, the enhancement of pharmacokinetic parameters of cisplatin loaded NH, compared with free cisplatin, revealed that the development of NH as a carrier system for cisplatin could be promising. Suitable nano size, relatively good hemo-compatibility, pH-responsive drug release pattern, active targeting via integrin receptors, and improvement of pharmacokinetic parameters are the exquisite features in this NH formulation.