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 advanced methods to measure temperature at the sub-micron level are therefore 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 (Nd-NCs) was optimized to achieve high photoluminescence (PL) intensity 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, showing excellent linearity and high thermal sensitivity. A silica shell was added to the particles and shown to confer excellent aqueous stability and biocompatibility in A549 lung cancer cells. Finally, luminescent thermal readout was demonstrated in vitro in A549 cells by spectrally resolving the diffraction-limited luminescence spots at a single-particle scale over a clinically relevant temperature range from 20-50 {degrees}C. The application of the developed nanothermometer as preclinical tools for NP-HT characterization could provide crucial information on the therapeutic temperature achieved in and around the tumor area. This could be key to optimizing NP properties and therapeutic parameters, for the development of viable hyperthermal cancer treatments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/579538v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1b06abdorg.highwire.dtl.DTLVardef@12fa23corg.highwire.dtl.DTLVardef@4439c1org.highwire.dtl.DTLVardef@12bcedd_HPS_FORMAT_FIGEXP M_FIG C_FIG