Synergistic Gas Therapy and Targeted Interventional Ablation With Size-Controllable Arsenic Sulfide (AsS) Nanoparticles for Effective Elimination of Localized Cancer Pain.

The elimination of localized cancer pain remains a globally neglected challenge. A potential solution lies in combining gas therapy with targeted interventional ablation therapy. In this study, HA-AsS nanoparticles with controlled sizes are synthesized using different molecular weights of sodium hyaluronate (HA) as a supramolecular scaffold. Initially, HA co-assembles with arsenic ions (As) via coordinate bonds, forming HA-As scaffold intermediates. These intermediates, varying in size, then react with sulfur ions to produce size-controlled HA-AsS particles. This approach demonstrates that different molecular weights of HA enable precise control over the particle size of arsenic sulfide, offering a straightforward and environmentally friendly method for synthesizing metal sulfide particles. In an acidic environment, HA-AsS nanoparticles release hydrogen sulfide(HS) gas and As. The released As directly damage tumor mitochondria, leading to substantial reactive oxygen species (ROS) production from mitochondria. Concurrently, the HS gas inhibits the activity of catalase (CAT) and complex IV, preventing the beneficial decomposition of ROS and disrupting electron transfer in the mitochondrial respiratory chain. Consequently, it is found that HS gas significantly enhances the mitochondrial damage induced by arsenic nanodrugs, effectively killing local tumors and ultimately eliminating cancer pain in mice.