2D Architectures-Transformed Conformational Nanoarchitectonics for Light-Augmented Nanocatalytic Chemodynamic and Photothermal/Photodynamic-Based Trimodal Therapies

The complexity of the cancer microenvironment makes it highly challenging for drugs to meet therapeutic requirements, significantly hampering their clinical translation. The enormous potential of intelligent materials that can act as drugs themselves results in the development of smart drugless or drug-like architectures, offering synergistic therapeutic effects. In this study, we demonstrate the generation of transition metal-based dichalcogenides (TMDCs)-based conformational (flower-like) nanoarchitectonics for synergistic trimodal therapies against breast carcinoma. Initially, the progressive transformation of two-dimensional (2D) molybdenum selenide (MoSe2)-based nanosheets into nanoflower-like architectures by the thermal injection method is observed with time. Further, these flowers are subsequently decorated with an optimal amount of platinum (Pt) nanoparticles for nanocatalytic efficacy and surface-modified with polyethylene glycol (PEG) for improved biocompatibility, shortly denoted as Pt-MoSe2-PEG for light-assisted photothermal (PTT) and photodynamic (PDT), as well as light-augmented chemodynamic (CDT) modalities. A series of physicochemical characterizations and performance validations successfully demonstrated the generation of tumor (pH/GSH)-responsive degradable nanoflower-like structures, substantially improving their ability of reactive oxygen species generation, MoSe2-based PTT/PDT capability, and light-augmented CDT efficacy of the Pt nanoenzymes. Finally, in vitro and in vivo investigations in the 4T1 cell line and its xenograft tumor model in BALB/C mice, respectively, validated the synergistic trimodal therapies of Pt-MoSe2-PEG toward ablating breast carcinoma.