Photostimulable Near-Infrared Persistent Luminescent Nanoprobes for Ultrasensitive and Longitudinal Deep-Tissue Bio-Imaging

Abstract

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr3+ near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr3+ nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

Chemically engineered persistent luminescence nanoprobes for bioimaging

“…Figure 20 shows a tumor targeting study where c(RGDyK)-conjugated LiGa 5 O 8 :Cr 3+ nanoparticles were intravenously injected into 4T1 tumor bearing mice. Good accumulation of the nanoparticles into the tumors could be observed after PSPL at 6 and 24 hours after injection (Figure 20) 97.…”

“…As discussed above in the manuscript, a solution to this problem would be to prepare a multimodal nanoprobe associating optical imaging to magnetic resonance imaging (MRI) 97. There are many reasons why MRI is preferred as a complementary modality to optical imaging in multimodal nanotools.…”

“…This is the reason why this phenomenon can be related to an optical battery where, filling the traps corresponds to the charging process. Then, in a second step corresponding to the discharge, the energy can be release by thermal or optical activation 23, 24 or by other physical stimulations such as mechano-stimulation for instance 25, resulting in stimulated emissions from the active centers [26, 27, 28 29, 30].…”

Long term in vivo imaging with Cr3+ doped spinel nanoparticles exhibiting persistent luminescence

“…In addition to thermal stimulation at ambient temperature (of the animal) as described above, charge release can also be induced by IR light stimulation. This is the so called photostimulated persistent luminescence (PSPL) [12,31]. The two types of stimulations are related to trap depth in the forbidden gap: charges from shallow traps can be released by animal temperature (persistent luminescence) while charge release from deep traps is only possible by IR irradiation through the animal body (PSPL).…”

“…This is the reason why this phenomenon can be related to an optical battery where, filling the traps corresponds to the charging process. Then, in a second step corresponding to the discharge, the energy can be released by thermal or optical stimulations [12,13], or by other physical stimulations (mechano-stimulation for instance [14]), resulting in light emissions from the optically active centers. Thus, emitters are the centers that emit in the wavelength range of interest, for example in the red and near infrared range for Bioimaging applications.…”