Traditional anticancer treatments fail to significantly improve prognoses, and exploration of novel promising therapeutic modalities is urgently needed. In this study, multifunctional mesoporous polydopamine nanoparticles (Pt@MPDA/GOx/Fe³⁺ NPs) loaded with glucose oxidase (GOx), Fe ions and ultrasmall Pt nanoparticles (NPs) were prepared for magnetic resonance imaging (MRI)-guided photothermal therapy (PTT)-enhanced chemodynamic therapy (CDT). The oxidation of intratumoral glucose to H₂O₂ and GOx induced an H₂O₂-rich microenvironment, and then elevated H₂O₂ was catalyzed into highly cytotoxic ·OH by Fe³⁺ via a Fenton reaction for CDT to induce cancer cell death efficiently. Notably, the heat generated by MPDA NPs under laser irradiation offered a moderate PTT to cascade the CDT effect. Moreover, Pt NPs can oxidize H₂O₂ to yield O₂, which in turn accelerates the catalytic process of GOx to increase the efficiency of CDT. Meanwhile, in the high oxidation environment of tumor cells, Pt NPs are oxidized into Pt²⁺ to achieve a tumor chemotherapy effect. In addition, chelated Fe³⁺ endows the system with an MRI-visible function to monitor the treatment efficacy. In conclusion, this study provides a novel MRI-guided PTT-enhanced CDT synergistic nanomedicine platform for cancer therapy.

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.