Thermal and redox responsive polyamidoamine dendrimer–poly(N‐isopropylacrylamide) bridged by disulfide linkages for targeted and controlled drug delivery system

Abstract

AbstractMultifactor‐responsive nanomaterials have been playing a vital role in drug delivery developments. Given the advantages of nanotechnology‐based systems, employing stimuli‐sensitive agents could offer a step forward to targeted drug delivery. Hence, we targeted to apply both thermal and redox‐sensitive agents, which are poly(N‐isopropylacrylamide) (PNIPAM) and disulfide, onto a classic platform polyamidoamine (PAMAM) dendrimer. In particular, PAMAM G3.5 was first grafted by an outermost layer composed of cystamine moieties and partially grafted with PNIPAM segments. This novel nanomaterial was successfully verified by FTIR, 1H NMR, and Raman spectroscopy. Besides, morphological and surface characteristics were observed by DLS, TEM, and zeta potential. Our novel drug delivery system displayed a spherical shape with a hydrodynamic size of 43.61 ± 6.04 nm at 37°C and 68.99 ± 4.69 nm at 15°C, which proved its thermoresponsiveness. In parallel, the response of the nanoparticles toward redox concentration variation was testified that demonstrated a controlled drug release highly depending on physiological stimuli. We have also conducted in vitro DOX release and cytocompatibility of this drug delivery system, which can premise a smart strategy for nanoengineering in targeted drug delivery for cancer therapy.