ROS-responsive polymeric micelles with aggregation-induced emission effects for drug delivery and cellular imaging

Traditional chemotherapy faces challenges related to limited drug efficacy and adverse reactions. Intelligent nanocarrier drug delivery systems (INDDSs) promise improved treatment outcomes with reduced toxicity. However, several clinical challenges persist in achieving rapid drug release and real-time monitoring. Herein, a ROS-responsive amphiphilic copolymer was synthesized: polyethylene glycol (mPEG-TK-OH) with ROS-responsive thioketal (TK) as the macromolecular initiator, and enzymatic ring-opening polymerization of caprolactone was performed. Small molecules of tetraphenylethylene (TPE) with aggregation-induced emission (AIE) properties were added to the polymer's terminus to enable fluorescence imaging and the ROS-responsive amphiphilic copolymer mPEG-TK-PCL-TPE with AIE properties is formed and enhances drug release monitoring through fluorescence resonance energy transfer (FRET) between TPE and the hydrophobic anti-cancer drug DOX. Leveraging distinct ROS levels between tumor and normal cells, these ROS-responsive nanomicelles effectively respond to high intracellular redox-active species and release DOX. The mPEG-TK-PCL-TPE micelles displayed a suitable size, high drug loading, and excellent imaging quality. In vitro cell experiments confirmed their biocompatibility and efficacy in inhibiting 4T1 tumor cells. This ROS-responsive amphiphilic copolymer, incorporating the AIE structure, introduces new opportunities for cancer treatment, enabling real-time drug release tracking and improving therapeutic outcomes. The ROS-responsive amphiphilic copolymer micelles mPEG-TK-PCL-TPE, combined with AIE properties, enable real-time drug release monitoring and intracellular tracing, and ensures stable circulation and rapid release in tumors.