Photodynamic therapy (PDT) has been extensively explored as a minimally invasive treatment strategy for malignant cancers. It works by a photosensitizer located within cancer cells is irradiated by near-infrared (NIR) light to produce potent toxins, singlet oxygen (1O2), and induce cell death. However, reactive oxygen species (ROS) can be over-expressed in tumor tissue due to 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, TEM, EDX, and DLS. 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 the nanoparticles could be biodegradable overtime in simulated body fluid (SBF), 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 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 4-fold tumor growth inhibition versus the control and more than two-fold over free Ce6 in orthotopic tumor xenografts. In addition, the oxygen saturation contrast inside tumors was evaluated by photoacoustic imaging (PAI) to demonstrate the alleviated hypoxia in vivo. Our works provide a novel nanosystem to ameliorate the hypoxic tumor microenvironment and augment the efficacy of PDT in targeted cancer treatment.

Biodegradable hollow manganese silicate nanocomposites to alleviate tumor hypoxia toward enhanced photodynamic therapy

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.