134 Hybrid Nanostructures Using Polymers to Reduce the Toxicity of Inorganic Luminescent Nanomaterials and Organic Dyes

Abstract There is a growing research effort to use polymers to encapsulate functional molecules and nanomaterials to control their beneficial effects and toxicity, by minimizing their interactions with biomolecules and organs outside of the target sites. This concept is well known as drug delivery systems using nanoparticles. A good example is the RNA vaccines that encapsulates highly degradable RNA in lipid nanoparticles and delivers RNAs stably to immune cells. Such strategies are expected to be effective in designing nanoscale materials with low toxicity. Here, we investigated a potential of inorganic and organic hybrid nanomaterials (HNMs) for photodynamic therapy (PDT) for lesions in deep tissues, by combining (1) dyes for PDT and (2) upconversion luminescent nanoparticles (UCL-NPs) that activate the dyes under irradiation with the light of near-infrared (NIR), which is in the biological window with high transparency in biological tissues. In this context, we designed an HNM in which a PDT dye, rose Bengal (RB), and UCL-NPs are encapsulated using biodegradable polymer nanoparticles. HNMs significantly reduced the toxicity of RB and protected NPs’ luminescence. By using ultrasmall UCL-NPs (<10 nm) for RB activation, the HNP was designed for UCL-NPs to be excreted via the kidneys. UCL-NPs also emit near-infrared (1550 nm) fluorescence, which enables imaging of deep tissues. Therefore, the PDT-HNM works as a “theranostic” probe to be used for PDT therapy while real-time monitoring the target location. The design of such nanostructures is expected to lead to further biomedical applications of molecular drugs as well as highly functional inorganic nanomaterials.