Innovative theranostic systems that provide high-quality P-gp blockade and near-infrared fluorescence imaging-guided chemo-photothermal therapy provide new perspectives on the development of novel multi-operational platforms and smart DDDs loaded with anticancer drugs with very good photothermal conversion for synergistic action of PDT, PTT and PIT, but also high-tech imaging and immunomodulatory properties in HCC. This evidence concerns the gene PGP and hepatocellular carcinoma.