Protein Shell-Encapsulated Pt Clusters as Continuous O₂-Supplied Biocoats for Photodynamic Therapy in Hypoxic Cancer Cells

As a highly oxygen-dependent process, the effect of photodynamic therapy is often obstructed by the premature leakage of photosensitizers and the lack of oxygen in hypoxic cancer cells. To overcome these limitations, this study designs bovine serum albumin protein (BSA)-encapsulated Pt nanoclusters (PtBSA) as O2-supplied biocoats and further incorporates them with mesoporous silica nanospheres to develop intelligent nanoaggregates for achieving improved therapeutic outcomes against hypoxic tumors. The large number of amino groups on BSA can provide sufficient functional groups to anchor tumor targeting agents and thus enhance the selective cellular uptake efficiency. Owing to the outstanding biocompatibility features of BSA and the state-of-the-art catalytic activity of Pt nanoclusters, the nanocomposites have lower dark cytotoxicity, and O2 continuously evolves via the decomposition of H2O2 in a tumor microenvironment. Both in vivo and in vitro experiments indicate that the resulting nanocomposites can effectively relieve hypoxic conditions, specifically induce necrotic cell apoptosis, and remarkably hinder tumor growth. Our results illuminate the great potential of BSA-encapsulated Pt nanoclusters as versatile biocoats in designing intelligent nanocarriers for hypoxic-resistant photodynamic therapy.