Fig. 1. Schematic showing the design of an orthogonally activatable CRISPR-Cas13d nanoprodrug for reversing chemoresistance and enhanced chemo-photodynamic therapy. (a) Chemical structure of the chemo-photodynamic prodrug and its photoactivation mechanism. (b) The orthogonal photoactivation of oxaliplatin prodrug-induced chemo-photodynamic therapy and Cas13d-mediated gene editing. (c) On-demand activation of the nanoprodrug with sequential MRP1 knockdown and efficient glutathione-mediated oxaliplatin(ii) release behavior for reversing drug resistance, resulting in enhanced combinational therapy in vivo.
