Development of a near infrared Au–Ag bimetallic nanocluster for ultrasensitive detection of toxic Pb2+ ions in vitro and inside cells

AbstractPhotothermal therapy (PTT) has attracted great interest in cancer treatment, and the quest for potential organic photothermal agents is underway owing to the nonbiodegradable nature and chronic toxicity of existing inorganic nanomaterials. Organic material-based nanoformulations with good photothermal and fluorescence properties in the near-infrared (NIR-I) window are scarce. However, porphyrins are one category of biocompatible systems that are advantageous for photothermal therapy but are currently based in the visible region, causing limited depth of tissue penetration and leading to compromised photothermal and near-infrared fluorescence (NIRF) imaging applications. To overcome these limitations, we report the synthesis of L,L-diphenylalanine conjugated BF2-oxasmaragdyrin (FF-BSC) and the fabrication of monodispersed spherical self-assemblies (FF-BSC NPs) using a USP class 3 solvent-water mixture. The resulting product exhibited excellent photostability (NIR exposure), multicycle photothermal efficacy, and NIR fluorescence. In vitro studies revealed good biocompatibility, efficient cellular internalization, and photothermal efficacy. Preclinical studies of these nano-self-assemblies demonstrated nontoxicity, efficient whole-body NIRF imaging, fractional passive tumor homing, and excellent photothermal tumor ablation potential. The absorbance and fluorescence of FF-BSC NPs in NIR-I make them suitable for theragnostic applications over existing porphyrins/inorganic nanomaterials for future clinical applications.

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Molecular Engineering for Boosting AIE-active Free Radical Photogenerator and Its High-performance in Hypoxia via Photodynamic Therapy

10.26434/chemrxiv.11826843.v1 ◽

2020 ◽

Author(s):

Qing Wan ◽

Rongyuan Zhang ◽

Zeyan Zhuang ◽

Yuxuan Li ◽

Zhiming Wang ◽

...

Keyword(s):

Free Radical ◽

High Performance ◽

Near Infrared ◽

Theoretical Calculations ◽

Tumor Hypoxia ◽

Molecular Engineering ◽

Type I ◽

Noninvasive Treatment ◽

Nir Fluorescence

<div> <p>Serious hypoxia in solid tumor as well as vicious aggregation-caused fluorescence quenching (ACQ) of conventional photosensitizers (PSs) limit the progress of the fluorescence imaging-guided photodynamic (PDT) although it has obvious advantages in precise spatial-temporal control and noninvasive treatment. The photosensitizers featuring Type I reactive oxygen species (ROS) based on free radical and novel aggregation-induced emission (AIE) characteristic (AIE-PSs) could offer precious opportunity to resolve above problems, but there was rare feasible molecular engineering in previous reports. Herein, we proposed that the strategy of fabricating stronger intermolecular charge transfer (ICT) effect in electron-rich anion-π<sup>+ </sup>AIE-active luminogens (AIEgens) aimed to help suppressing nonradiative internal conversion (IC) as well as promote radiative and intersystem crossing (ISC) processes for boosting more free radical generation. Systematic and detailed experimental and theoretical calculations proved our ideas when the electron-donating abilities enhanced in collaborative donors, and the AIE-PSs exhibited higher performance in near-infrared red (NIR) fluorescence image-guided cancer PDT <i>in vitro/vivo</i>. This work would become an important reference to the design of AIE-active free radical generators for overcoming ACQ effect and tumor hypoxia in future PDT.</p> </div>

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Validation of a Three-Dimensional Head and Neck Spheroid Model to Evaluate Cameras for NIR Fluorescence-Guided Cancer Surgery

International Journal of Molecular Sciences ◽

10.3390/ijms22041966 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1966

Author(s):

Claire Egloff-Juras ◽

Ilya Yakavets ◽

Victoria Scherrer ◽

Aurélie Francois ◽

Lina Bezdetnaya ◽

...

Keyword(s):

Head And Neck ◽

Near Infrared ◽

Tumor Model ◽

Resection Margins ◽

Fluorescence Signal ◽

Multicellular Tumor Spheroid ◽

Guided Surgery ◽

Nir Fluorescence ◽

Fluorescence Guided Surgery

Near-infrared (NIR) fluorescence-guided surgery is an innovative technique for the real-time visualization of resection margins. The aim of this study was to develop a head and neck multicellular tumor spheroid model and to explore the possibilities offered by it for the evaluation of cameras for NIR fluorescence-guided surgery protocols. FaDu spheroids were incubated with indocyanine green (ICG) and then included in a tissue-like phantom. To assess the capability of Fluobeam® NIR camera to detect ICG in tissues, FaDu spheroids exposed to ICG were embedded in 2, 5 or 8 mm of tissue-like phantom. The fluorescence signal was significantly higher between 2, 5 and 8 mm of depth for spheroids treated with more than 5 µg/mL ICG (p < 0.05). The fluorescence intensity positively correlated with the size of spheroids (p < 0.01), while the correlation with depth in the tissue-like phantom was strongly negative (p < 0.001). This multicellular spheroid model embedded in a tissue-like phantom seems to be a simple and reproducible in vitro tumor model, allowing a comparison of NIR cameras. The ideal configuration seems to be 450 μm FaDu spheroids incubated for 24 hours with 0.05 mg/ml of ICG, ensuring the best stability, toxicity, incorporation and signal intensity.

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Molecular Engineering for Boosting AIE-active Free Radical Photogenerator and Its High-performance in Hypoxia via Photodynamic Therapy

10.26434/chemrxiv.11826843 ◽

2020 ◽

Author(s):

Qing Wan ◽

Rongyuan Zhang ◽

Zeyan Zhuang ◽

Yuxuan Li ◽

Zhiming Wang ◽

...

Keyword(s):

Free Radical ◽

High Performance ◽

Near Infrared ◽

Theoretical Calculations ◽

Tumor Hypoxia ◽

Molecular Engineering ◽

Type I ◽

Noninvasive Treatment ◽

Nir Fluorescence

<div> <p>Serious hypoxia in solid tumor as well as vicious aggregation-caused fluorescence quenching (ACQ) of conventional photosensitizers (PSs) limit the progress of the fluorescence imaging-guided photodynamic (PDT) although it has obvious advantages in precise spatial-temporal control and noninvasive treatment. The photosensitizers featuring Type I reactive oxygen species (ROS) based on free radical and novel aggregation-induced emission (AIE) characteristic (AIE-PSs) could offer precious opportunity to resolve above problems, but there was rare feasible molecular engineering in previous reports. Herein, we proposed that the strategy of fabricating stronger intermolecular charge transfer (ICT) effect in electron-rich anion-π<sup>+ </sup>AIE-active luminogens (AIEgens) aimed to help suppressing nonradiative internal conversion (IC) as well as promote radiative and intersystem crossing (ISC) processes for boosting more free radical generation. Systematic and detailed experimental and theoretical calculations proved our ideas when the electron-donating abilities enhanced in collaborative donors, and the AIE-PSs exhibited higher performance in near-infrared red (NIR) fluorescence image-guided cancer PDT <i>in vitro/vivo</i>. This work would become an important reference to the design of AIE-active free radical generators for overcoming ACQ effect and tumor hypoxia in future PDT.</p> </div>

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Retro-enantio isomer of angiopep-2 assists nanoprobes across the blood-brain barrier for targeted magnetic resonance/fluorescence imaging of glioblastoma

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00724-y ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Ruoxi Xie ◽

Zijun Wu ◽

Fanxin Zeng ◽

Huawei Cai ◽

Dan Wang ◽

...

Keyword(s):

Magnetic Resonance ◽

Fluorescence Imaging ◽

Near Infrared ◽

Ex Vivo ◽

Malignant Gliomas ◽

Resonance Fluorescence ◽

Malignant Tumours ◽

Nir Fluorescence

AbstractGlioblastoma (GBM), one of the most common primary intracranial malignant tumours, is very difficult to be completely excised by surgery due to its irregular shape. Here, we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles (SPIONs) modified with indocyanine (Cy7) molecules and peptides (ANG or DANG) to locate malignant gliomas and guide accurate excision. Both peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro, and both could mediate precise aggregation of the nanoprobes at gliomas sites in in vivo magnetic resonance imaging (MRI) and ex vivo near-infrared (NIR) fluorescence imaging. However, compared with ANG/Cy7-SPIONs probes, DANG/Cy7-SPIONs probes exhibited better enhanced MR imaging effects. Combining all these features together, this MRI/NIR fluorescence imaging dual-modal nanoprobes modified with retro-enantio isomers of the peptide have the potential to accurately display GBMs preoperatively for precise imaging and intraoperatively for real-time imaging.

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Targeted Nanoparticles for Fluorescence Imaging of Folate Receptor Positive Tumors

Biomolecules ◽

10.3390/biom10121651 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1651

Author(s):

Aimee J. Marko ◽

Ballav M. Borah ◽

Kevin E. Siters ◽

Joseph R. Missert ◽

Anurag Gupta ◽

...

Keyword(s):

Folic Acid ◽

Fluorescence Imaging ◽

Near Infrared ◽

Folate Receptor ◽

Cyanine Dye ◽

Target Specificity ◽

Nir Fluorescence ◽

Positive Breast Cancer

This report presents the synthesis and folate receptor target-specificity of amino-functionalized polyacrylamide nanoparticles (AFPAA NPs) for near-infrared (NIR) fluorescence imaging of cancer. For the synthesis of desired nano-constructs, the AFPAA NPs (hereafter referred to as NPs) were reacted with a NIR cyanine dye (CD) bearing carboxylic acid functionality by following our previously reported approach, and the resulting conjugate (NP-CD) on further reaction with folic acid (FA) resulted in a new nano-construct, FA-NP-CD, which demonstrated significantly higher uptake in folate receptor-positive breast cancer cells (KB+) and in folate receptor over-expressed tumors in vivo. The target-specificity of these nanoparticles was further confirmed by inhibition assay in folate receptor-positive (KB+) and -negative (HT-1080) cell lines. To show the advantages of polyacrylamide (PAA)-based NPs in folate receptor target-specificity, the CD used in preparing the FA-NP-CD construct was also reacted with folic acid alone and the synthetic conjugate (CD-FA) was also investigated for its target-specificity. Interestingly, in contrast to NPs (FA-NP-CD), the CD-FA conjugate did not show any significant in vitro or in vivo specificity toward folate receptors, showing the advantages of PAA-based nanotechnology in delivering the desired agent to tumor cells.

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Formulation of Folate-Modified Raltitrexed-Loaded Nanoparticles for Colorectal Cancer Theranostics

Pharmaceutics ◽

10.3390/pharmaceutics12020133 ◽

2020 ◽

Vol 12 (2) ◽

pp. 133 ◽

Cited By ~ 3

Author(s):

Justin G. Rosch ◽

Allison N. DuRoss ◽

Madeleine R. Landry ◽

Conroy Sun

Keyword(s):

Colorectal Cancer ◽

Near Infrared ◽

Ex Vivo ◽

Cell Uptake ◽

Layer By Layer ◽

Nir Fluorescence ◽

Theranostic Applications ◽

Cancer Theranostics

Multifunctional nanoparticles (NPs) that enable the imaging of drug delivery and facilitate cancer cell uptake are potentially powerful tools in tailoring oncologic treatments. Here we report the development of a layer-by-layer (LbL) formulation of folic acid (FA) and folate antimetabolites that have been well-established for enhanced tumor uptake and as potent chemotherapeutics, respectively. To investigate the uptake of LbL coated NPs, we deposited raltitrexed (RTX) or combined RTX-FA on fluorescent polystyrene NPs. The performance of these NP formulations was evaluated with CT26 murine colorectal cancer (CRC) cells in vitro and in vivo to examine both uptake and cytotoxicity against CRC. Fluorescence microscopy and flow cytometry indicated an increased accumulation of the coated NP formulations versus bare NPs. Ex vivo near-infrared (NIR) fluorescence imaging of major organs suggested the majority of NPs accumulated in the liver, which is typical of a majority of NP formulations. Imaging of the CRC tumors alone showed a higher average fluorescence from NPs accumulated in animals treated with the coated NPs, with the majority of RTX NP-treated animals showing the consistently-highest mean tumoral accumulation. Overall, these results contribute to the development of LbL formulations in CRC theranostic applications.

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In vitro and in vivo NIR Fluorescence Lifetime Imaging with a time-gated SPAD camera

10.1101/2021.12.26.474189 ◽

2021 ◽

Author(s):

Jason T. Smith ◽

Alena Rudkouskaya ◽

Shan Gao ◽

Juhi M. Gupta ◽

Arin Ulku ◽

...

Keyword(s):

Fluorescence Lifetime ◽

Near Infrared ◽

Single Photon ◽

In Vivo Studies ◽

Fluorescence Lifetime Imaging ◽

Iccd Camera ◽

Lifetime Imaging ◽

Nir Fluorescence

Near-infrared (NIR) fluorescence lifetime imaging (FLI) provides a unique contrast mechanism to monitor biological parameters and molecular events in vivo. Single-photon avalanche photodiode (SPAD) cameras have been recently demonstrated in FLI microscopy (FLIM) applications, but their suitability for in vivo macroscopic FLI (MFLI) in deep tissues remains to be demonstrated. Herein, we report in vivo NIR MFLI measurement with SwissSPAD2, a large time-gated SPAD camera. We first benchmark its performance in well-controlled in vitro experiments, ranging from monitoring environmental effects on fluorescence lifetime, to quantifying Förster Resonant Energy Transfer (FRET) between dyes. Next, we use it for in vivo studies of target-drug engagement in live and intact tumor xenografts using FRET. Information obtained with SwissSPAD2 was successfully compared to that obtained with a gated-ICCD camera, using two different approaches. Our results demonstrate that SPAD cameras offer a powerful technology for in vivo preclinical applications in the NIR window.

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Infrared fluorescence lymphography in experimental and clinical practice

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2018-17-2-84-91 ◽

2018 ◽

Vol 17 (2) ◽

pp. 84-91 ◽

Cited By ~ 1

Author(s):

G. V. Papayan ◽

A. L. Akopov ◽

P. A. Antonyan ◽

A. A. Ilin ◽

N. N. Petrishchev

Keyword(s):

Lymph Nodes ◽

Near Infrared ◽

Lymphatic System ◽

Lymphatic Vessels ◽

Diagnostic System ◽

Biological Tissues ◽

Peritumoral Injection ◽

Intradermal Administration ◽

Nir Fluorescence ◽

Real Time Visualization

Introduction. Near infrared (NIR) fluorescent diagnostics is promising due to a deeper penetration into biological tissues. Material and methods. In experiments on rabbits and in clinical studies evaluation the lymphatic system with the use of the instrument complex FLUM-808 was analysed. Results. For visualization of the lymphatic vessels of the skin, the intradermal administration of ICG, dissolved in 20 % albumin in the order of 0.02 mg/ml, is optimal. Peritumoral injection of ICG allows visualizing sentinel lymph nodes in patients with lung cancer. Conclusions. The developed NIR fluorescence diagnostic system FLUM-808 allows to real time visualization of lymphatic vessels and lymph nodes.

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