Chain-shattering polymeric sulfur dioxide prodrug micelles for redox-triggered gas therapy of osteosarcoma

Sulfur dioxide (SO₂) based gas therapy has received great attention recently. Nevertheless, it is still a challenge to fabricate a SO₂ delivery system to achieve effective delivery and on-demand stimuli triggered release at tumor sites. Herein, a chain-shattering polymeric SO₂ prodrug micelle system was fabricated for effective SO₂ based gas therapy. First, an amphiphilic polymer (mPEG-P(HDI-DN)) was prepared by polycondensation of poly(ethylene glycol) methyl ether, hexamethylene diisocyanate and monomer containing SO₂. mPEG-P(HDI-DN) can self-assemble into spherical micelles with a diameter of around 50-90 nm. Triggered release of SO₂ from micelles can be achieved in the presence of GSH with the degradation of mPEG-P(HDI-DN) into small molecules. The in vitro experiment proved that mPEG-P(HDI-DN) micelles can enter into osteosarcoma cells and inhibit the growth of osteosarcoma cells by increasing the ROS level in cells. The in vivo experiments demonstrate that mPEG-P(HDI-DN) micelles can inhibit the growth of osteosarcoma effectively without obvious tissue toxicity. These results indicate that this chain-shattering polymeric SO₂ prodrug micelle system is a promising candidate for effective SO₂ based gas therapy.