Silica-Coated Ga(III)-Doped ZnO: Yb3+, Tm3+ Upconversion Nanoparticles for High-Resolution in Vivo Bioimaging using Near-Infrared to Near-Infrared Upconversion Emission

Abstract Upconversion nanoparticles (UCNPs) are a promising nanoplatform for bioreagent formation for in vivo imaging, which emit UV and blue light under the action of near-infrared radiation, providing deep tissue penetration and maintaining a high signal-to-noise ratio. In the case of solid tumor visualization, the UCNP surface functionalization is required to ensure a long circulation time, biocompatibility, and non-toxicity. The effective UCNP accumulation in the solid tumors is determined by the disturbed architecture of the vascular network and lymphatic drainage. This work demonstrates an approach to the UCNP biofunctionalization with endogenous polysialic acid for in vivo bioreagent formation. Bioreagents possess a low level of nonspecific protein adsorption and macrophage uptake, which allow the prolongation of the circulation time in the bloodstream up to 3 h. This leads to an intense photoluminescent signal in the tumor.

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Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, In Vitro Toxicity, and In Vivo Imaging Studies

Nanomaterials ◽

10.3390/nano11092234 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2234

Author(s):

Anbharasi Lakshmanan ◽

Roman A. Akasov ◽

Natalya V. Sholina ◽

Polina A. Demina ◽

Alla N. Generalova ◽

...

Keyword(s):

Near Infrared ◽

Therapeutic Potential ◽

Ex Vivo ◽

Laboratory Animals ◽

In Vitro Toxicity ◽

Upconversion Nanoparticles ◽

Lewis Lung Cancer ◽

Spectral Bands

Formulation of promising anticancer herbal drug curcumin as a nanoscale-sized curcumin (nanocurcumin) improved its delivery to cells and organisms both in vitro and in vivo. We report on coupling nanocurcumin with upconversion nanoparticles (UCNPs) using Poly (lactic-co-glycolic Acid) (PLGA) to endow visualisation in the near-infrared transparency window. Nanocurcumin was prepared by solvent-antisolvent method. NaYF4:Yb,Er (UCNP1) and NaYF4:Yb,Tm (UCNP2) nanoparticles were synthesised by reverse microemulsion method and then functionalized it with PLGA to form UCNP-PLGA nanocarrier followed up by loading with the solvent-antisolvent process synthesized herbal nanocurcumin. The UCNP samples were extensively characterised with XRD, Raman, FTIR, DSC, TGA, UV-VIS-NIR spectrophotometer, Upconversion spectrofluorometer, HRSEM, EDAX and Zeta Potential analyses. UCNP1-PLGA-nanocurcumin exhibited emission at 520, 540, 660 nm and UCNP2-PLGA-nanocurmin showed emission at 480 and 800 nm spectral bands. UCNP-PLGA-nanocurcumin incubated with rat glioblastoma cells demonstrated moderate cytotoxicity, 60–80% cell viability at 0.12–0.02 mg/mL marginally suitable for therapeutic applications. The cytotoxicity of UCNPs evaluated in tumour spheroids models confirmed UCNP-PLGA-nanocurcumin therapeutic potential. As-synthesised curcumin-loaded nanocomplexes were administered in tumour-bearing laboratory animals (Lewis lung cancer model) and showed adequate contrast to enable in vivo and ex vivo study of UCNP-PLGA-nanocurcumin bio distribution in organs, with dominant distribution in the liver and lungs. Our studies demonstrate promise of nanocurcumin-loaded upconversion nanoparticles for theranostics applications.

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PAA Modified Upconversion Nanoparticles for Highly Selective and Sensitive Detection of Cu2+ Ions

Frontiers in Chemistry ◽

10.3389/fchem.2020.619764 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shaoshan Su ◽

Zhurong Mo ◽

Guizhen Tan ◽

Hongli Wen ◽

Xiang Chen ◽

...

Keyword(s):

Near Infrared ◽

Upconversion Emission ◽

Upconversion Nanoparticles ◽

Highly Sensitive ◽

Carboxylate Complex ◽

Sensitivity And Selectivity ◽

Uv Visible ◽

Emission Quenching ◽

Co Precipitation ◽

Higher Sensitivity

Detection of the Cu2+ ions is crucial because of its environmental and biological implications. The fluorescent-based organic sensors are not suitable for Cu2+ detection due to their short penetration depth caused by the UV/visible excitation source. Therefore, we have demonstrated a highly sensitive and selective near-infrared (NIR) excitable poly(acrylic acid) (PAA) coated upconversion nanoparticles (UCNPs) based sensor for Cu2+ detection. We construct the PAA modified Na(Yb, Nd)F4@Na(Yb, Gd)F4:Tm@NaGdF4 core-shell-shell structured UCNPs based sensor via a co-precipitation route. The upconversion emission intensity of the PAA-UCNPs decreases linearly with the increase in the Cu2+ concentration from 0.125 to 3.125 μM due to the copper carboxylate complex formation between Cu2+ and PAA-UCNPs. The calculated detection limit of the PAA-UCNPs based sensor is 0.1 μM. The PAA-UCNPs based sensor is very sensitive and selective toward detecting the Cu2+ ions, even when the Cu2+ co-exist with other metal ions. The EDTA addition has significantly reversed the upconversion emission quenching by forming the EDTA-Cu2+ complex based on their greater affinity toward the Cu2+. Therefore, the PAA-UCNPs based sensor can be a promising candidate for Cu2+ detection because of their higher sensitivity and selectivity under 980 nm NIR excitation.

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Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe

Circulation ◽

10.1161/circ.142.suppl_3.14935 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Dong Oh Kang ◽

Yong Geun Lim ◽

Joon Woo Song ◽

Ye Hee Park ◽

Hyun Jung Kim ◽

...

Keyword(s):

Molecular Imaging ◽

High Resolution ◽

Murine Model ◽

Calcium Binding ◽

Laser Scanning ◽

Near Infrared ◽

Imaging System ◽

Whole Body ◽

Imaging Results

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p<0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p<0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.

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Hyaluronate modified upconversion nanoparticles for near infrared light-triggered on–off tattoo systems

RSC Advances ◽

10.1039/c6ra28600c ◽

2017 ◽

Vol 7 (24) ◽

pp. 14805-14808 ◽

Cited By ~ 1

Author(s):

Seulgi Han ◽

Songeun Beack ◽

Sanghwa Jeong ◽

Byung Woo Hwang ◽

Myeong Hwan Shin ◽

...

Keyword(s):

Biomedical Applications ◽

Near Infrared ◽

Infrared Light ◽

Upconversion Nanoparticles ◽

Near Infrared Light ◽

Nir Light

We successfully developed an NIR light-triggered in vivo on–off tattoo system using hyaluronate modified upconversion nanoparticles for various biomedical applications.

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Hemicyanine-based High Resolution Ratiometric near-Infrared Fluorescent Probe for Monitoring pH Changes in Vivo

Analytical Chemistry ◽

10.1021/ac5045498 ◽

2015 ◽

Vol 87 (4) ◽

pp. 2495-2503 ◽

Cited By ~ 145

Author(s):

Yinhui Li ◽

Yijun Wang ◽

Sheng Yang ◽

Yirong Zhao ◽

Lin Yuan ◽

...

Keyword(s):

High Resolution ◽

Fluorescent Probe ◽

Near Infrared ◽

Ph Changes

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First In Vivo Use of High-Resolution Near-Infrared Optical Mapping to Assess Atrial Activation During Sinus Rhythm and Atrial Fibrillation in a Large Animal Model

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.118.006870 ◽

2018 ◽

Vol 11 (12) ◽

Cited By ~ 4

Author(s):

Brian J. Hansen ◽

Ning Li ◽

Katelynn M. Helfrich ◽

Suhaib H. Abudulwahed ◽

Esthela J. Artiga ◽

...

Keyword(s):

Atrial Fibrillation ◽

Animal Model ◽

High Resolution ◽

Sinus Rhythm ◽

Near Infrared ◽

Optical Mapping ◽

Large Animal Model ◽

Large Animal ◽

Atrial Activation

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In vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig models

Cardiovascular Research ◽

10.1093/cvr/cvz039 ◽

2019 ◽

Vol 115 (11) ◽

pp. 1659-1671 ◽

Cited By ~ 11

Author(s):

Peter Lee ◽

Jorge G Quintanilla ◽

José M Alfonso-Almazán ◽

Carlos Galán-Arriola ◽

Ping Yan ◽

...

Keyword(s):

High Resolution ◽

Cardiac Electrophysiology ◽

High Speed ◽

Near Infrared ◽

Optical Mapping ◽

Ex Vivo ◽

Average Rate ◽

Camera System ◽

Epicardial Surface

Abstract Aims Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. Methods and results First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63–138) cm/s vs. 51 (41–64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217–254) ms vs. 192 (182–233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min−1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. Conclusions In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.

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Ultra-stable near-infrared Tm3+-doped upconversion nanoparticles for in vivo wide-field two-photon angiography with a low excitation intensity

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545819500135 ◽

2019 ◽

Vol 12 (03) ◽

pp. 1950013 ◽

Cited By ~ 1

Author(s):

Wen Liu ◽

Runze Chen ◽

Sailing He

Keyword(s):

Power Density ◽

Near Infrared ◽

Multilayer Coating ◽

Excitation Power ◽

Whole Body ◽

Upconversion Nanoparticles ◽

Excitation Power Density ◽

Two Photon ◽

Coating Method

Two-photon luminescence with near-infrared (NIR) excitation of upconversion nanoparticles (NPs) is of great importance in biological imaging due to deep penetration in high-scattering tissues, low auto-luminescence and good sectioning ability. Unfortunately, common two-photon luminescence is in visible band with an extremely high exciation power density, which limits its application. Here, we synthesized NaYF4:Yb[Formula: see text]Tm@NaYF4 upconversion NPs with strong two-photon NIR emission and a low excitation power density. Furthermore, NaYF4:Yb[Formula: see text]Tm@NaYF4@SiO2@OTMS@F127 NPs with high chemical stability were obtained by a modified multilayer coating method which was applied to upconversion NPs for the first time. In addition, it is shown that the as-prepared hydrophillic upconversion NPs have great biocompatibility and kept stable for 6 hours during in vivo whole-body imaging. The vessels with two-photon luminescence were clear even under an excitation power density as low as 25[Formula: see text]mW[Formula: see text]cm2. Vivid visualizations of capillaries and vessels in a mouse brain were also obtained with low background and high contrast. Because of cheaper instruments and safer power density, the NIR two-photon luminescence of NaYF4:Yb[Formula: see text]Tm@NaYF4 upconversion NPs could promote wider application of two-photon technology. The modified multilayer coating method could be widely used for upconversion NPs to increase the stable time of the in vivo circulation. Our work possesses a great potential for deep imaging and imaging-guided treatment in the future.

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