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Hepatocellular carcinoma (HCC) is a life-threatening disease for which there is no effective treatment currently. Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy. Herein, we develop the sialic acid (SA) modified polymeric micelles at an upper critical solution temperature (UCST) of 43 °C (sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile), SA-PEG-p(AAm-co-AN)), which further encapsulated with doxorubicin (DOX) and Gd-CuS nanoparticles (Gd-CuS NPs) for chemo-photothermal treatment of HCC guided by magnetic resonance (MR)/photoacoustic (PA) dual-mode imaging. The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS (SPDG) had an excellent photothermal conversion efficiency, enabling SPDG with an instantaneous release behavior of DOX under near-infrared (NIR) irradiation. This study also revealed that SPDG could actively target to HCC, which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site. Moreover, benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX, SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment. Overall, our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.
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