A mini-review on rare-earth down-conversion nanoparticles for NIR-II imaging of biological systems

Rare-earth(RE)based luminescent probes exhibit rich optical properties including upconversion and down-conversion luminescence spanning a broad spectral range from 300 to 3,000 nm,and have generated great scientific and practical interest from telecommunication to biological imaging.While upconversion nanoparticles have been investigated for decades,down-conversion luminescence of RE-based probes in the second near-infrared(NIR-II,1,000-1,700 nm)window for in vivo biological imaging with sub-centimeter tissue penetration and micrometer image resolution has come into light only recently.In this review,we present recent progress on RE-based NIR-II probes for in vivo vasculature and molecular imaging with a focus on Er3+-based nanoparticles due to the down-conversion luminescence at the long-wavelength end of the NIR-II window(NIR-IIb,1,500-1,700 nm).Imaging in NIR-IIb is superior to imaging with organic probes such as ICG and IRDye800 in the^800 nm NIR range and the 1,000-1,300 nm short end of NIR-II range,owing to minimized light scattering and autofluorescence background.Doping by cerium and other ions and phase engineering of Er^3+-based nanoparticles,combined with surface hydrophilic coating optimization can afford ultrabright,biocompatible NIR-IIb probe towards clinical translation for human use.The Nd^3+-based probes with NIR-II emission at 1,050 and 1,330 nm are also discussed,including Nd^3+doped nanocrystals and Nd^3+-organic ligand complexes.This review also points out future directions for further development of multi-functional RE NIR-II probes for biological imaging.

A theranostic agent for cancer therapy and imaging in the second nearinfrared window

Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.