GSH/pH-sensitive Förster resonance energy transfer nanoparticles for synergistic chemotherapy and chemodynamic therapy

Abstract

Stimulus-responsive polymers have attracted significant attention as intelligent and advanced drug delivery systems. In this work, a glutathione-responsive polymer was synthesized by reversible addition–fragmentation chain transfer polymerization of natural biological molecules lipoic acid and tetraphenylene (TPE)-containing vinyl monomers. The poly(disulfide) block ensures rapid degradation of carriers and drug release under specific conditions. In addition, the introduction of pendant carboxyl groups enables Fe³⁺ incorporating capacity and the hydrophobic TPE block significantly boosts drug loading and aggregation induced emission (AIE) for visualization of assembly. Fe³⁺ and doxorubicin (DOX) loaded nanoparticles (DOX@Fe NPs) were obtained via coordination and hydrophobic interactions for synergistic chemodynamic therapy and chemotherapy. Especially, the Förster resonance energy transfer (FRET) between TPE and DOX further enables visualization of DOX release via a fluorescence signal. The in vitro release experiment results demonstrated that under the conditions of pH 5.5 and 5 mM GSH, the release efficiency of DOX reached 79.2% in 12 hours. In the cellular experiment, the viability of 4T1 cells co-incubated with DOX@Fe NPs for 48 hours was only 2.5%, verifying that DOX@Fe NPs possess potent tumor-killing capability.