Designing Programmable MOF-nanocomposites for Synergistic, Redox-Driven Antitumor Therapies

Cancer remains one of the most pressing global health challenges, with current therapies often limited by toxicity, hypoxia, and lack of spatial precision. Photo-bioMOF addresses these barriers by pioneering a new generation of multifunctional nanoMOFs for fully integrated multimodal cancer therapy. The project introduces an unprecedented design: direct incorporation of Au(III) into MOF linkers, enabling the in situ formation of photoactive AuNPs within the tumor microenvironment. In parallel, introducing a heavy metal (e.g. Hf4+) into the clusters lowers the HOCO–LUCO band gap, amplifying light absorption, boosting ROS generation, and enhancing radiosensitivity under irradiation. By unifying these 2 mechanisms within a single framework, Photo-bioMOF will create a platform where photothermal, photodynamic, and radiotherapeutic functions converge, while also enabling irradiation-triggered chemotherapy release—achieving, for the first time, a fully integrated 4-in-1 nanomedicine. Beyond chemical innovation, the project establishes proof of concept through a staged validation pipeline: in vitro studies on pulmonary cells (host), ex vivo testing in patient-derived 3D lung organoids (secondment), and in ovo evaluation using vascularized tumor models (non-academic placement). This workflow ensures robust assessment of efficacy, biodistribution, and safety, while consolidating the fellow’s expertise in MOF design and providing outstanding training in nanotechnology, biological validation, and translational nanomedicine—strengthening independence and leadership potential. By initially targeting lung cancer the project addresses an unmet medical need, while its design principles are adaptable to other cancers or diseases (e.g. infections). In parallel, the structural and photochemical versatility of nanoMOFs enables applications in energy and environment (e.g. photocatalysis, decontamination, sensing), positioning Photo-bioMOF at the frontier of translational nanoscience.