Unveiling Lithium Doping-Driven Morphological and Optical Modulation in Highly Water-Dispersible NaYF4:Ho,Yb Upconversion Nanoparticles for Super-Bright Imaging

Abstract A series of highly crystalline and uniform-sized monodisperse Li+ codoped NaYF4:Ho3+, Yb3+ (YHYL) nanoparticles are successfully synthesized via a thermolysis approach by varying Li+ (0–15 at %) and Yb3+ (0–20 at %) concentrations. Li+ doping not only increases the crystallite size but also enhances the luminescence intensity by 60 times. Upon excitation with a 980 nm laser, it produces a super-bright green emission. Highly water-dispersible nanoparticles are obtained by a two-step ligand exchange method with five different capping agents, which have their own characteristic features in biomedical applications. HCl-washed NaYF4:2 at % Ho3+, 20 at % Yb3+, 10 at % Li+ (YHYL-10-HCl) nanoparticles exhibit high biocompatibility in the WI-26 normal human cell line and can therefore be utilized for ex vivo imaging, anticounterfeiting, and noncontact-based optical temperature sensors under NIR excitation. After chitosan coating, YHYL-10-chitosan nanoparticles demonstrate enhanced biocompatibility in the MCF-7 cancer cell line, as well as impressive hemocompatibility in human blood. Hence, chitosan-coated YHY, YHYL-2, and YHYL-10 nanoparticles are subsequently evaluated for multiphoton in vitro imaging, including Z-stack 3D imaging, suggesting internalization of chitosan-coated nanoparticles in MCF-7 and A549 cancer cell lines under 980 nm laser excitation.