Biocompatible Neodymium-Doped Nanocrystals as Probes for Diffraction-limited, in vitro Temperature Sensing

Abstract

Localized hyperthermia is a promising approach to cancer therapy. However, its clinical potential is limited by heterogeneous heat distribution within tumors, and improved methods to measure temperature at the sub-micron level are required. To address this challenge, luminescent nanothermometers, such as lanthanide-doped nanocrystals (Ln-NC) operating in the near-infrared (NIR), have been investigated for accurate spatiotemporal thermal monitoring. In this study, the synthesis of neodymium-doped, sodium yttrium fluoride nanocrystals (NaYF4) was optimized to achieve high photoluminescence (PL) under NIR irradiation by adjusting the dopant concentration and by shelling with inert layers. Standard curves for luminescence-based temperature readout were developed using ratiometric analysis of the temperature-dependent PL spectra in the 850-920 nm biological window. A silica shell was added to the particles and shown to confer excellent aqueous stability and cellular uptake in A549 lung cancer cells, with cell viability maintained >85% when incubated with up to 50 ug/ml of the silica-shelled particles over 6 hours. Finally, luminescent thermal readout was demonstrated in vitro in A549 cells by spectrally resolving the diffraction-limited luminescence spots from single particles over a clinically relevant temperature range from 20-50 C. The demonstration of biocompatible, nanoscale, NIR thermometry in cells is a significant step in the development of viable hyperthermal cancer treatments.