Fig. 4. Orthogonal regulation of MRP1 by using the Cas13d nanoprodrug. (a) Schematic illustration of overcoming MRP1-mediated drug resistance upon activation of the nanoprodrug with 808 nm light. (b) Relative MRP1 mRNA expression in HCT116/L-OHP cells post-incubation with URL and harvested at 6 h after 980 or 808 nm treatment. ***P < 0.001 and ****P < 0.0001. (c) Western blot analysis of MRP1 expression in HCT116/L-OHP cells post-incubation with URL and harvested at 12 h after 980 or 808 nm treatment. (d) Quantitative densitometric analysis of MRP1 levels shown in (c). Data are means ± SE (n = 3). (e) CLSM images of HCT116/L-OHP cells with indicated treatments. Scale bar: 20 μm.