Efficient ROS activation by highly stabilized aqueous ICG encapsulated upconversion nanoparticles for tumor cell imaging and therapeutics

Abstract

Dye-sensitized upconversion nanoparticles (UCNPs) have gained significant interest in biological applications. However, previous attempts to utilize these dye-sensitized UCNPs in the aqueous environment suffer from dramatic decline in the upconversion luminescence (UCL) intensity and problems with nanoparticles aggregation and water quenching. By employing indocyanine green (ICG) as a hydrophobic amplifier and energy harvester for UCNPs, we use a general, facile, and kinetically controlled mixing technology—flash nanoprecipitation (FNP)—to prepare aqueous stable ICG-sensitized UCNPs encapsulated by a biocompatible block copolymer poly (ethylene glycol)-b-poly (lactic-co-glycolic acid (PEG-b-PLGA) to efficiently activate ROS generation for simultaneous cancer cell imaging and treatment. As compared to NPs obtained from traditional drip and stir method (TM), the NPs under high turbulent conditions (high Re) exhibit smaller size, narrower size distribution, and much higher stability, for the UCNPs hydrophobicity enhanced by ICG which was bound on the surface of UCNPs due to the coordination effect between sulfonates of ICG molecules and naked lanthanide metal ions of UCNPs. The remained UCL intensity was significantly boosted as well as ROS generation through FNP in the presence of ICG, but not for TM samples indicating superior protection of upconversion NPs from water quenching and the energy transfer between ICG and UCNP was well retained. The efficiency of ROS generation of NPs via FNP evidently increases with the stronger red-light emission of UCNPs, resulting in high cytotoxicity for SMMC-7721 cells in vitro and good suppression of tumor growth in vivo. The success of NPs by FNP in biological application demonstrates a bright prospect of FNP for synthesis of efficient antitumor nanoparticles.