Engineering Two-dimensional tungsten-doped molybdenum selenide transformed conformational nanoarchitectonics: Trimodal therapeutic nanoagents for enhanced synergistic Photothermal/Chemodynamic/Chemotherapy of breast carcinoma.

Two-dimensional transition metal dichalcogenides (TMDCs) exhibit promising photothermal therapy (PTT) and chemodynamic therapy (CDT) for anti-tumour treatment. Herein, we proposed an engineering strategy to regulate the lattice structure of tungsten-doped molybdenum selenide (MoWSe) transformed conformational nanoarchitectonics using a microwave-assisted solvothermal method for enhancing peroxidase (POD)-like catalytic performance by adjusting the ratio of molybdenum (Mo) and tungsten (W). Furthermore, the optimised MoWSe nanoflakes surface was modified with chitosan (CHI) for improved biocompatibility and nanocatalytic efficacy, then the obtained CHI-MoWSe subsequently loaded the chemotherapeutic drug mitoxantrone (MTO) for enhanced 4 T1 cells killing ability, shortly denoted as CHI-MoWSe-MTO for PTT-augmented CDT and chemotherapy (CT). A series of performance validations successfully showed that electrons tend to transfer from W to Mo in CHI-MoWSe, which resulted in superior POD-like activity (Km = 0.038 mM) of CHI-MoWSe compared with that of horseradish peroxidase. Furthermore, CHI-MoWSe-MTO with excellent photothermal conversion efficiency (PCE=63.2 %) in the near-infrared (NIR) region could further promote endogenous •OH generation and MTO controlled release within solid tumours. In vivo studies confirmed the successful achievement of synergistic therapeutic effects (tumour inhibition rate of over 90 %) with minimised side effects. Versatile therapeutic nanoagents hold great potential for personalised therapy of breast cancer and will find their way to the pharmaceutical field.