Two-dimensional porous vermiculite-based nanocatalysts for synergetic catalytic therapy

This study reports an ultrasound-mediated and two-dimensional (2D) porous vermiculite nanosheets (VMT NSs)-based nanocatalyst platform (Arg@VMT@PDA-PEG) that synergistically harnessed the Fenton reaction-based chemodynamic therapy (CDT), 2D semiconductor-based sonodynamic therapy (SDT) and nitric oxide (NO)-based gas therapy for combination cancer therapy. The tumor microenvironment responsive degradation of polydopamine (PDA) shell could not only prevent L-Arg, a NO donor, leakage during blood circulation, but also selectively release the active sites of VMT NSs for catalytic reactions in tumor cells. Additionally, the Fenton reactions mediated by the abundant Fe²⁺/Fe³⁺ in VMT NSs could efficiently produce ·OH and consume glutathione (GSH) for CDT. Moreover, the reactive oxygen species (ROS, ·OH and ·O₂^-) produced by ultrasound-triggered Arg@VMT@PDA-PEG could not only execute SDT but also oxidize L-Arg to NO for synergetic gas therapy. The results show that the transformation of ROS to NO can enhance curative efficacy owing to the ability of NO with much longer life-time in freely diffusing into cells from intercellular space. This biodegradable Arg@VMT@PDA-PEG nanocatalytic platform integrating three different catalytic reactions provides a new therapeutic paradigm for combination cancer therapy.