Oxygen Self‐Enriched Nanophotosensitizers Based On Hollow Mesoporous Silica Nanoparticles for Enhanced Photodynamic Therapy

In practical tumor treatments, the therapeutic efficacy of photodynamic therapy (PDT) is undermined due to the restricted generation of reactive oxygen species (ROS) in the hypoxic tumor microenvironment. Hence, tumor oxygenation is considered as an effective strategy to improve PDT outcome. In this work, oxygen self‐enriched nanophotosensitizers (PFH@NPSs) are facilely constructed based on hollow mesoporous silica nanoparticles, in which photosensitizer and oxygen‐supplier perfluorohexane (PFH) are coloaded. The as‐prepared PFH@NPSs exhibited uniform size distribution (68.2 ± 2.1 nm), large cavity diameter (≈55.8 nm), high drug loading efficiency (≈10 wt%), and excellent oxygen reservoir capacity (164.4 μmol g − 1 ). In vitro PDT is then performed on HeLa cells with 405 nm photoirradiation, and under hypoxic conditions, PFH@NPSs produced 4.4‐fold higher singlet oxygen quantum yield than that of NPSs without PFH, which can still efficiently kill tumor cells with a cell viability of 43.3%. This study establishes PFH@NPSs as a translatable platform for overcoming hypoxia‐driven PDT resistance, offering a dual‐action mechanism of targeted oxygen delivery and amplified ROS generation.