Eosin Y-Functionalized Upconverting Nanoparticles: Nanophotosensitizers and Deep Tissue Bioimaging Agents for Simultaneous Therapeutic and Diagnostic Applications

SIMPLE SUMMARY: This work describes a nanoplatform for deep-tissue photodynamic therapy (PDT) and imaging using upconverting nanoparticles functionalized with eosin Y (EY), a photosensitizer (PS) that have been demonstrated to be effective even in hypoxic environments. These structures take advantage of the capability of the nanoparticles to be excited by 800 nm near infrared light, where penetration is higher in comparison with visible light commonly used in PDT, and the thermal load is minimum. Additionally, the combination with UCNPs enables the transport of EY into the cell, which is not possible for EY alone. The generation of reactive oxygen species (ROS) under 800 nm light inside the cell becomes therefore possible based on upconversion and energy transfer processes. These UCNPs also present long lasting infrared fluorescence under 808 nm excitation, thus enabling their use as deep tissue bioimaging agent during PDT. ABSTRACT: Functionalized upconverting nanoparticles (UCNPs) are promising theragnostic nanomaterials for simultaneous therapeutic and diagnostic purposes. We present two types of non-toxic eosin Y (EY) nanoconjugates derived from UCNPs as novel nanophotosensitizers (nano-PS) and deep-tissue bioimaging agents employing light at 800 nm. This excitation wavelength ensures minimum cell damage, since the absorption of water is negligible, and increases tissue penetration, enhancing the specificity of the photodynamic treatment (PDT). These UCNPs are uniquely qualified to fulfil three important roles: as nanocarriers, as energy-transfer materials, and as contrast agents. First, the UCNPs enable the transport of EY across the cell membrane of living HeLa cells that would not be possible otherwise. This cellular internalization facilitates the use of such EY-functionalized UCNPs as nano-PS and allows the generation of reactive oxygen species (ROS) under 800 nm light inside the cell. This becomes possible due to the upconversion and energy transfer processes within the UCNPs, circumventing the excitation of EY by green light, which is incompatible with deep tissue applications. Moreover, the functionalized UCNPs present deep tissue NIR-II fluorescence under 808 nm excitation, thus demonstrating their potential as bioimaging agents in the NIR-II biological window.