Photodynamic therapy (PDT) has been extensively explored as a minimally invasive treatment strategy for malignant cancers. It works with the help of a photosensitizer located within cancer cells that is irradiated by near-infrared light to produce potent toxins and singlet oxygen (1O2) and induce cell death. However, reactive oxygen species can be overexpressed in tumor tissue because of the rapid metabolic activity in cancer cells, and the insufficient oxygenation (hypoxia) can lead to low production of singlet oxygen (1O2) during PDT. In this study, we developed nanocomposites composed of a hollow manganese silicate (HMnOSi) nanoparticle and a photosensitizer (Ce6) that can generate significant amounts of O2 to relieve tumor hypoxia and enhance the therapeutic efficacy of PDT. Our nanocomposites were characterized by UV–vis, fluorescence spectroscopy, transmission electron microscopy (TEM), energy-dispersive X-ray, and dynamic light scattering. Our particles’ hollow mesoporous structures were shown to retain large amounts of Ce6 on the particle surface with high loading capacity (33%). TEM imaging showed that the nanoparticles could be biodegradable over time in simulated body fluid, which can imply clinical potentials. Significant H2O2 quenching capabilities to alleviate hypoxic conditions in a solid tumor were also presented. For breast cancer cells, the nanocomposite-treated group revealed that 91% of cells were dead under laser activation compared to 51% for the control group (free Ce6). In an animal study, our nanocomposites showed almost fourfold tumor growth inhibition versus the control and more than twofold over free Ce6 in orthotopic tumor xenografts. In addition, the oxygen saturation contrast inside tumors was evaluated by photoacoustic imaging to demonstrate the alleviated hypoxia in vivo. Our works provide a smart nanosystem to ameliorate the hypoxic tumor microenvironment and augment the efficacy of PDT in a targeted cancer treatment.

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