Sub 20 nm Upconversion Photosensitizers for Near‐Infrared Photodynamic Theranostics

Abstract Efficient type II photodynamic therapy (PDT) requires stable and biocompatible photosensitizers (PS) that present low dark cytotoxicity, are photo‐excitable in deep tissue regions, and can efficiently penetrate and kill cells via in situ singlet oxygen production. Here, heavy‐metal‐free organic PS are combined with near‐infrared (NIR)‐excitable small (<20 nm) upconversion nanoparticles (UCNPs) into UCNP‐PS nanohybrids for accomplishing such advanced PDT conditions. UCNP‐to‐PS energy transfer efficiencies between 11% and 42% and 1 O 2 generation quantum yields between 74% and 86% resulted in efficient NIR‐sensitized PDT. HeLa cells incubated with UCNP‐PS can be efficiently destroyed via 808 nm laser irradiance at 140 mW cm −2 for 3 min (<30% cell viability) or 3.2 W cm −2 for 6 min (<10% cell viability). Theranostic functionality of UCNP‐PS is demonstrated via live cell in situ imaging of intracellular UCNP‐PS‐mediated 1 O 2 production, which resulted in cell death, most probably via apoptosis. Preliminary in vivo experiments are also performed and the consequences for a detailed in vivo study toward clinical translation are discussed. The combined PDT and deep‐tissue imaging properties of the nanomolecular PS present a large potential for future implementation into advanced in vivo photodynamic theranostics.