Rational Design of Self-Reporting Polymersomes for the Controlled Release of Sulfur Dioxide

As a new member of the gaseous regulators, sulfur dioxide (SO₂) plays a crucial role in many biological activities. Recent studies have shown that SO₂ is capable of inducing cancer cell apoptosis by regulating intracellular reactive oxygen species (ROS), allowing SO₂ to serve as an efficient therapeutic agent. Although various polymer-based platforms have presented great potential for the controlled release of SO₂, most of the systems are incapable of monitoring the intracellular generation of SO₂. In this work we present the rational design of SO₂-releasing biodegradable polymersomes, accompanied by a self-reporting property. The polymersome consists of a hydrophilic block of poly(ethylene glycol) (PEG) and a hydrophobic segment of poly(trimethylene carbonate) (PTMC)-based SO₂ donors. The polymersomes not only exhibit good SO₂-releasing performance upon treatment with glutathione (GSH), but can also regulate the fluorescence change of the system, offering a good platform for real-time monitoring of the intracellular production of SO₂. Significantly, the in vitro and in vivo studies indicate the potential for exploitation of these polymersomes as antitumor agents. We expect that incorporating both the SO₂-releasing capacity and self-reporting feature within a polymersome system will provide a unique opportunity for the development of intelligent gas nanovehicles.