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

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 <i>via</i> 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 <i>via</i> a fluorescence signal. The <i>in vitro</i> 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.