Preparation of dual-targeted redox-responsive nanogels based on pegylated sorbitan for targeted and antitumor drug delivery

Abstract

This work reports the synthesis and use of a new functionalized biocompatible disulfide nanogel system based on magnetite pegylated sorbitan (PEGS), cross-linked with the amino acid N,N’-di(tert-butoxycarbonyl) cystine (N-Boc-cystine) and conjugated with folic acid (FA), to be used asan application in drug delivery systems. To achieve this purpose, Fe3O4 nanoparticles were prepared via a co-precipitation method. Star-shaped PEG that was coupled with 3-aminopropyl triethoxysilane via a Michael reaction, was grafted on the surface of iron oxide nanoparticles. The terminal hydroxyl groups on the PEG-S chain, asan efficient functional group, would easily be further modified with specific and effective groups such asactive targeting and/or cross-link agents. The carbodiimide coupling chemistry was used to conjugate FA and bind the cross-linker. To demonstrate the accuracy of each step, the structures were characterized using Fourier transform infrared spectroscopy (FTIR) spectroscopy. Thermal analysis was performed to confirm the formation of PEGS graft on the surface of the magnetite. Particle size, zeta potential and nanoparticles colloidal stability were determined by dynamic light scattering. The in vitro release behavior of 5-Fluorouracil asan anticancer drug from nanogels was investigated at pH 7.4 in phosphate-buffered saline (PBS). Folated nanogel displayed high cellular uptake into DU145 cell lines, which are distinguishable from folate-free one.