Hepatoblastoma (HB) has a subtle onset and poor prognosis in high-risk group patients. Due to the adverse reactions and drug resistance associated with traditional systemic chemotherapy, there is an urgent need for new treatment strategies. Photothermal therapy (PTT) has been proposed as an advanced, patient-centered approach for cancer treatment. However, the safety concerns regarding traditional photothermal agents and the existence of intracellular self-protective autophagy mechanisms have hindered the clinical application and efficacy of PTT. This paper reports the development of a two-dimensional (2D) MXene-based composite nanoplatform for efficient synergistic autophagy inhibition and PTT for HB. Here, by directly coating a mesoporous silica layer on the surface of 2D Nb2C MXene nanosheets, the hydrophilicity/dispersion was enhanced. An autophagy inhibitor nanogenerator was designed, wherein the mesopores provide a reservoir for the autophagy inhibitor chloroquine (CQ), and the MXene core acts as a photothermal trigger under a near-infrared II (NIR-II) biowindow. In vitro experimental results showed that CQ/Nb2C@MSNs-PEG, after entering the tumor, induced rapid release of the encapsulated CQ to inhibit pro-survival autophagy in cells under 1064 nm NIR-II laser irradiation, enhancing the photothermal cytotoxicity of Nb2C@MSNs-PEG on tumor cells. Importantly, the CQ/Nb2C@MSNs-PEG therapeutic platform demonstrated effective antitumor activity in the HuH-6 tumor-bearing mouse model, validating the synergistic strategy of PTT and protective autophagy blockade for enhanced efficacy. This study provides a promising strategy for hepatoblastoma treatment by combining autophagy inhibition to enhance the photothermal therapeutic effect.
Huang et al. (Wed,) studied this question.