Huijuan Liang

Using 915 nm Laser Excited Tm3+/Er3+/Ho3+-Doped NaYbF4 Upconversion Nanoparticles for in Vitro and Deeper in Vivo Bioimaging without Overheating Irradiation

Successful further development of superhigh-constrast upconversion (UC) bioimaging requires addressing the existing paradox: 980 nm laser light is used to excite upconversion nanoparticles (UCNPs), while 980 nm light has strong optical absorption of water and biological specimens. The overheating caused by 980 nm excitation laser light in UC bioimaging is computationally and experimentally investigated for the first time. A new promising excitation approach for better near-infrared to near-infrared (NIR-to-NIR) UC photoluminescence in vitro or in vivo imaging is proposed employing a cost-effective 915 nm laser. This novel laser excitation method provides drastically less heating of the biological specimen and larger imaging depth in the animals or tissues due to quite low water absorption. Experimentally obtained thermal-graphic maps of the mouse in response to the laser heating are investigated to demonstrate the less heating advantage of the 915 nm laser. Our tissue phantom experiments and simulations verified that the 915 nm laser is superior to the 980 nm laser for deep tissue imaging. A novel and facile strategy for surface functionalization is utilized to render UCNPs hydrophilic, stable, and cell targeting. These as-prepared UCNPs were characterized by TEM, emission spectroscopy, XRD, FTIR, and zeta potential. Specifically targeting UCNPs excited with a 915 nm laser have shown very high contrast UC bioimaging. Highly stable DSPE-mPEG-5000-encapsulated UCNPs were injected into mice to perform in vivo imaging. Imaging and spectroscopy analysis of UC photoluminescence demonstrated that a 915 nm laser can serve as a new promising excitation light for UC animal imaging.

Upconversion Emission Enhancement in Yb3+/Er3+-Codoped Y2O3 Nanocrystals by Tridoping with Li+ Ions

We demonstrate that tridoping with Li + ions enhances the visible green and red upconversion (UC) emissions in Er 3+ /Yb 3+ -codoped Y 2 O 3 nanocrystals by up to half of the bulk counterpart, i.e., about 2 orders of magnitude higher than previous results. X-ray diffraction and decay time investigations give evidence that tridoping with Li + ions can tailor the local crystal field of the Y 2 O 3 host lattice. Theoretical calculations illustrate well that a significant UC intensity enhancement arises from the synthesized tailoring effect induced by the Li + ions, which increase lifetimes in the intermediate 4 I 11/2 (Er) and 2 F 5/2 (Yb) states, increase optically active sites in the Y 2 O 3 host lattice, and dissociate the Yb 3+ and Er 3+ ion clusters in the nanocrytals. The general theoretical description of the visible UC radiations shows that the Yb 3+ ion sensitization and the tailoring effect induced by the Li + ions are two independent enhancement mechanisms, which is expected to lead to an increasing number of photonic and biomedical applications in the future.

Upconversion emission tuning from green to red in Yb3+/Ho3+-codoped NaYF4 nanocrystals by tridoping with Ce3+ ions.

Upconversion (UC) emission tuning from green to red in monodisperse NaYF(4):Yb(3+)/Ho(3+) nanocrystals was successfully achieved by tridoping with Ce(3+) ions under diode laser excitation of 970 nm. It is proposed that two efficient cross-relaxation processes, 5S2/5F4(Ho) + 2F(5/2)(Ce) --> 5F5(Ho) + 2F(7/2)(Ce) and 5I6(Ho) + 2F(5/2)(Ce) --> 5I7(Ho) + 2F(7/2)(Ce)between Ho(3+) and Ce(3+) ions, have been employed to select UC pathways to tune the UC radiation. Theoretical investigations based on steady-state equations demonstrate the proposed UC mechanisms and explain well the observed linear increase of the UC red-to-green intensity ratio with the increment of Ce(3+) ion concentrations.

Enhancement of the upconversion radiation in Y2O3:Er3+ nanocrystals by codoping with Li+ ions

We report on an innovative route to increase the upconversion (UC) green radiation by two orders of magnitude in Y2O3:Er3+ nanocrystals through tailoring Er3+ ions’ local environment with Li+ ions under diode laser excitation of 970nm. Theoretical investigations based on the steady-state rate equations indicate that such enhancement arises from a combining effect of the tailored lifetime of the intermediate I11∕24(Er) state, the suppressed cross relaxation H11∕22(Er)+I15∕24(Er)→I9∕24(Er)+I13∕24(Er) process, and the enlarged nanocrystal size induced by the Li+ ions. The proposed route here may constitute a promising step to solve the low efficiency problem in UC materials.

Autofluorescence insensitive imaging using upconverting nanocrystals in scattering media

Autofluorescence is a nuisance in the field of fluorescence imaging and tomography of exogenous molecular markers in tissue, degrading the quality of the collected data. In this letter, we report autofluorescence insensitive imaging using highly efficient upconverting nanocrystals (NaYF4:Yb3+∕Tm3+) in a tissue phantom illuminated with near-infrared radiation of 85mW∕cm2. It was found that imaging with such nanocrystals leads to an exceptionally high contrast compared to traditional downconverting fluorophores due to the absence of autofluorescence. Upconverting nanocrystals may be envisaged as important biological markers for tissue imaging purposes.

Near vacuum ultraviolet luminescence of Gd3+ and Er3+ ions generated by super saturation upconversion processes

Near vacuum ultraviolet (UV) upconversion (UC) emissions with a spectral resolution of 1 nm, from the (6)G(J), (6)D(J), (6)I(J), (6)P(J) levels of Gd(3+) and the (2)L(17/2), (4)D(7/2), (2)H(2)(9/2), (2)D(5/2), (4)G(7/2), (2)K(13/2), (2)P(3/2) levels of Er(3+), were observed under 974 nm laser excitation. Mechanism analyses illustrate that successive energy transfers (ETs) from Yb(3+) to Er(3+) generate UV UC radiations in Er(3+), while two resonant ETs from Er(3+) to Gd(3+) lead to UV UC radiations in Gd(3+). Power dependence analyses indicate that the expected inefficient four- and five-photon processes have been switched into efficient two-photon processes due to a super saturation UC phenomenon that employs consecutive saturations at the intermediate states.

Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery of rabbits

Photodynamic therapy (PDT) has been applied in the treatment of artery restenosis following balloon injury. This study aimed to detect the accumulation of 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PpIX) in inflamed atherosclerotic plaque in rabbit model and evaluate the efficacy of PDT. The inflamed atherosclerotic plaque in the common carotid artery was produced by combination of balloon denudation injury and high cholesterol diet. After intravenous administration of ALA, the fluorescence of PpIX in plaque was detected. At the peak time, the correlation between the fluorescence intensity of PpIX and the macrophage infiltration extent in plaque was analyzed. Subsequently, PDT (635nm at 50J/cm(2)) on the atherosclerotic plaques (n=48) was performed and its effect was evaluated by histopathology and immunohistochemistry. The fluorescence intensity of PpIX in the plaque reached the peak 2h after injection and was 12 times stronger than that of adjacent normal vessel segment, and has a positive correlation with the macrophage content (r=0.794, P<0.001). Compared with the control group, the plaque area was reduced by 59% (P<0.001) at 4week after PDT, the plaque macrophage content decreased by 56% at 1week and 64% at 4week respectively, the smooth muscle cells (SMCs) was depleted by 24% at 1week (P<0.05) and collagen content increased by 44% at 4week (P<0.05). It should be pointed out that the SMC content increased by 18% after PDT at 4week compared with that at 1week (P<0.05). Our study demonstrated that the ALA-derived PpIX can be detected to reflect the macrophage content in the plaque. ALA mediated PDT could reduce macrophage content and inhibit plaque progression, indicating a promising approach to treat inflamed atherosclerotic plaques.

Ultraviolet-blue upconversion emissions of Ho 3+ ions

Ultraviolet-blue upconversion (UC) radiations of Ho3+ ions at 240, 290, 360, 385, 418, 445, 485 nm were observed in hexagonal NaYF4:Yb3+∕Ho3+ powders under diode laser excitation of 970 nm. UC mechanism analyses illustrate that successive energy transfers from Yb3+ to Ho3+ generate emissions at 240, 360, 385, and 418 nm, while cross relaxations between Ho3+ ions evoke UC emissions at 290 and 445 nm. Power dependence analyses indicate that these UC emissions already have intense saturation effects even at low-power density range of 0.3–38 W∕cm2. Theoretical calculations based on steady-state equations demonstrate the proposed UC mechanisms and explain well the observed saturation effects.

Anomalous power dependence of upconversion emissions in Gd2O3:Er3+ nanocrystals under diode laser excitation of 970 nm

Visible green and red upconversion (UC) emissions with anomalous power dependence were observed in Gd2O3:Er3+ nanocrystals at room temperature under diode laser excitation of 970 nm. The green and red UC radiations both yield an “s”-shape power dependence, in marked contrast to the quadratic ones of the bulk counterparts. A closed positive looping UC mechanism that differs from conventional PA mechanism is proposed to explain the observed five- or six-photon processes in the “s”-shape power dependence. Power dependence analysis of the 1.55 μm emissions from the I413/2 state experimentally demonstrates our proposed model.

Hematoporphyrin monomethyl ether-mediated photodynamic effects on THP-1 cell-derived macrophages

Photodynamic therapy (PDT) has been shown to attenuate atherosclerotic plaque progression and decrease macrophage-infiltration. The effectiveness of PDT depends strongly on the type of photosensitizers. Hematoporphyrin monomethyl ether (HMME) is a promising second-generation porphyrin-related photosensitizer for PDT. This study is designed to characterize effects of HMME-based PDT on THP-1 cell-derived macrophages and define the cell-death pathway. HMME was identified to accumulate in the macrophages by fluorescence microscopy and confocal scanning laser microscope. Our data demonstrated that the intensity of laser-induced HMME fluorescence in macrophages steadily increased with the increasing incubation concentration of HMME. The survival rate of macrophages determined by MTT assay decreased with the increasing HMME concentration and irradiation time. HMME-based PDT induced macrophage apoptosis via caspase-9 and caspase-3 activation pathway detected by caspase fluorescent assay kit and flow cytometer. The PDT increased the number of apoptotic macrophages by 14-fold at 12 h post irradiation by 9 J/cm(2) 635 nm diode laser. These results imply that photodynamic therapy with HMME may therefore be a useful clinical treatment for unstable atherosclerotic plaques.