scholarly journals Targeted theranostic photoactivation on atherosclerosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Joon Woo Song ◽  
Jae Won Ahn ◽  
Min Woo Lee ◽  
Hyun Jung Kim ◽  
Dong Oh Kang ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Near Infrared ◽  
Scavenger Receptor ◽  
Plaque Burden ◽  
Light Illumination ◽  
Murine Models ◽  
Tyrosine Protein Kinase ◽  
Scavenger Receptor A ◽  
Kinase Expression

Abstract Background Photoactivation targeting macrophages has emerged as a therapeutic strategy for atherosclerosis, but limited targetable ability of photosensitizers to the lesions hinders its applications. Moreover, the molecular mechanistic insight to its phototherapeutic effects on atheroma is still lacking. Herein, we developed a macrophage targetable near-infrared fluorescence (NIRF) emitting phototheranostic agent by conjugating dextran sulfate (DS) to chlorin e6 (Ce6) and estimated its phototherapeutic feasibility in murine atheroma. Also, the phototherapeutic mechanisms of DS-Ce6 on atherosclerosis were investigated. Results The phototheranostic agent DS-Ce6 efficiently internalized into the activated macrophages and foam cells via scavenger receptor-A (SR-A) mediated endocytosis. Customized serial optical imaging-guided photoactivation of DS-Ce6 by light illumination reduced both atheroma burden and inflammation in murine models. Immuno-fluorescence and -histochemical analyses revealed that the photoactivation of DS-Ce6 produced a prominent increase in macrophage-associated apoptotic bodies 1 week after laser irradiation and induced autophagy with Mer tyrosine-protein kinase expression as early as day 1, indicative of an enhanced efferocytosis in atheroma. Conclusion Imaging-guided DS-Ce6 photoactivation was able to in vivo detect inflammatory activity in atheroma as well as to simultaneously reduce both plaque burden and inflammation by harmonic contribution of apoptosis, autophagy, and lesional efferocytosis. These results suggest that macrophage targetable phototheranostic nanoagents will be a promising theranostic strategy for high-risk atheroma. Graphical abstract

scholarly journals The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1819
Author(s):  
Michael A. Turner ◽  
Thinzar M. Lwin ◽  
Siamak Amirfakhri ◽  
Hiroto Nishino ◽  
Robert M. Hoffman ◽  
...  
Keyword(s):  
Near Infrared ◽  
Fluorescent Dyes ◽  
Review Article ◽  
In Vivo Studies ◽  
Murine Models ◽  
Exclusion Criteria ◽  
Major Barrier ◽  
Tumor Margins ◽  
Cancer Types

A major barrier to the diagnosis and effective treatment of solid-tumor cancers is the difficulty in detection and visualization of tumor margins in primary and metastatic disease. The use of fluorescence can augment the surgeon’s ability to detect cancer and aid in its resection. Several cancer types express carcinoembryonic antigen (CEA) including colorectal, pancreatic and gastric cancer. Antibodies to CEA have been developed and tagged with near-infrared fluorescent dyes. This review article surveyed the use of CEA antibodies conjugated to fluorescent probes for in vivo studies since 1990. PubMed and Google Scholar databases were queried, and 900 titles and abstracts were screened. Fifty-nine entries were identified as possibly meeting inclusion/exclusion criteria and were reviewed in full. Forty articles were included in the review and their citations were screened for additional entries. A total of 44 articles were included in the final review. The use of fluorescent anti-CEA antibodies has been shown to improve detection and resection of tumors in both murine models and clinically. The cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer.

scholarly journals Injectable and Temperature-Sensitive Titanium Carbide-Loaded Hydrogel System for Photothermal Therapy of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Yao ◽  
Chuanda Zhu ◽  
Tianjiao Peng ◽  
Qiang Ma ◽  
Shegan Gao
Keyword(s):  
Titanium Carbide ◽  
Cancer Treatment ◽  
Photothermal Therapy ◽  
Therapeutic Strategy ◽  
Near Infrared ◽  
Pluronic F127 ◽  
Temperature Sensitive ◽  
Hydrogel System

Recently, organic–inorganic hybrid materials have gained much attention as effective photothermal agents for cancer treatment. In this study, Pluronic F127 hydrogel-coated titanium carbide (Ti3C2) nanoparticles were utilized as an injectable photothermal agent. The advantages of these nanoparticles are their green synthesis and excellent photothermal efficiency. In this system, lasers were mainly used to irradiate Ti3C2 nanoparticles to produce a constant high temperature, which damaged cancer cells. The nanoparticles were found to be stable during storage at low temperatures for at least 2 weeks. The Ti3C2 nanoparticles exhibited a shuttle-shaped structure, and the hydrogels presented a loosely meshed structure. In addition, Ti3C2 nanoparticles did not affect the reversible temperature sensitivity of the gel, and the hydrogel did not affect the photothermal properties of Ti3C2 nanoparticles. The in vitro and in vivo results show that this hydrogel system can effectively inhibit tumor growth upon exposure to near-infrared irradiation with excellent biocompatibility and biosafety. The photothermal agent-embedded hydrogel is a promising photothermal therapeutic strategy for cancer treatment by enhancing the retention in vivo and elevating the local temperature in tumors.

Abstract 14893: Light Activation in Plaque Macrophages Enhances Efferocytosis of Apoptotic Cells via Upregulation of Autophagy and Mertk Expression

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joon Woo Song ◽  
Min Woo Lee ◽  
Hyun Jung Kim ◽  
Jiseon Min ◽  
Un Gyo Kang ◽  
...  
Keyword(s):  
Specific Binding ◽  
Scavenger Receptor ◽  
Fold Increase ◽  
Foam Cells ◽  
Protective Role ◽  
Plaque Burden ◽  
Apoptotic Cells ◽  
Light Activation ◽  
Theranostic Agent

Introduction: Autophagy plays a protective role in atherosclerosis and can promote efferocytosis of apoptotic cells. Photoactivation is a promising tool for treating cardiovascular disease, and induces autophagy in macrophages-derived foam cells, however, regulation of autophagy and efferocytosis by photoactivation in atherosclerotic plaque remains unknown. Objective: The present study aims to investigate whether macrophage targeted light activation induces autophagy and enhances efferocytosis in inflamed plaques Methods and Results: Targeted photoactivatable agent showed specific binding affinity and phototoxicity to scavenger receptor-expressing macrophages. Confocal microscopy analysis over time after irradiation demonstrated the induction of apoptosis and autophagy flux in macrophage-derived foam cells. The theranostic agent localized to macrophage scavenger receptors within atherosclerotic plaques, and intravital fluorescence microscopy imaged plaque inflammation and was used to monitor photobleaching after irradiation. Serial in vivo imaging analysis demonstrated that macrophage-specific photoactivation reduced plaque burden and inflammation after 1 week (Figure A). Mechanistically, targeted light activation induced autophagy within atheroma as early as 1 day (Figure B), and increased phagocytic receptor Mer tyrosine kinase (MerTK) expression. Targeted photoactivation had 2-fold-increase in macrophage-associated apoptotic bodies at one week after laser irradiation, indicating enhanced efferocytosis (Figure C). Conclusions: As a sensitive multifunctional therapeutic and imaging strategy, macrophage targeted photoactivation with autophagy induction could confer a promising theranostic strategy for the high-risk plaques.

scholarly journals Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal Pathogen Pneumocystis carinii

2007 ◽  
Vol 75 (8) ◽  
pp. 3999-4005 ◽  
Author(s):  
Melissa Hollifield ◽  
Elsa Bou Ghanem ◽  
Willem J. S. de Villiers ◽  
Beth A. Garvy
Keyword(s):  
Alveolar Macrophages ◽  
Pneumocystis Carinii ◽  
Scavenger Receptor ◽  
Interleukin 12 ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Scavenger Receptor A

ABSTRACT Alveolar macrophages are the effector cells largely responsible for clearance of Pneumocystis carinii from the lungs. Binding of organisms to β-glucan and mannose receptors has been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance of P. carinii, mice deficient in the expression of scavenger receptor A (SRA) were infected with P. carinii, and clearance of organisms was monitored over time. SRA-deficient (SRAKO) mice consistently cleared P. carinii faster than did wild-type control mice. Expedited clearance corresponded to elevated numbers of activated CD4+ T cells in the alveolar spaces of SRAKO mice compared to wild-type mice. Alveolar macrophages from SRAKO mice had increased expression of CD11b on their surfaces, consistent with an activated phenotype. However, they were not more phagocytic than macrophages expressing SRA, as measured by an in vivo phagocytosis assay. SRAKO alveolar macrophages produced significantly more tumor necrosis factor alpha (TNF-α) than wild-type macrophages when stimulated with lipopolysaccharide in vitro but less TNF-α in response to P. carinii in vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF-α, interleukin 12 (IL-12), and IL-18 in response to P. carinii infection than did wild-type mice. Together, these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context of P. carinii infection.

scholarly journals NIR-II emissive AIEgen photosensitizers enable ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ruizhen Jia ◽  
Han Xu ◽  
Chenlu Wang ◽  
Lichao Su ◽  
Jinpeng Jing ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Near Infrared ◽  
Liver Tumors ◽  
Early Stage ◽  
Oxygen Species ◽  
Hepatic Tumors ◽  
Primary Liver Tumors ◽  
Guided Surgery

AbstractAccurate diagnosis and effective treatment of primary liver tumors are of great significance, and optical imaging has been widely employed in clinical imaging-guided surgery for liver tumors. The second near-infrared window (NIR-II) emissive AIEgen photosensitizers have attracted a lot of attention with higher-resolution bioimaging and deeper penetration. NIR-II aggregation-induced emission-based luminogen (AIEgen) photosensitizers have better phototherapeutic effects and accuracy of the image-guided surgery/phototherapy. Herein, an NIR-II AIEgen phototheranostic dot was proposed for NIR-II imaging-guided resection surgery and phototherapy for orthotopic hepatic tumors. Compared with indocyanine green (ICG), the AIEgen dots showed bright and sharp NIR-II emission at 1250 nm, which extended to 1600 nm with high photostability. Moreover, the AIEgen dots efficiently generated reactive oxygen species (ROS) for photodynamic therapy. Investigations of orthotopic liver tumors in vitro and in vivo demonstrated that AIEgen dots could be employed both for imaging-guided tumor surgery of early-stage tumors and for ‘downstaging’ intention to reduce the size. Moreover, the therapeutic strategy induced complete inhibition of orthotopic tumors without recurrence and with few side effects. Graphical Abstract

Abstract 225: Anti-atherosclerotic Effects of Plaque Macrophage Targetable Nanoparticle-mediated PPAR-γ Agonist Delivery in Atherogenic Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jah Yeon Choi ◽  
Jiheun Ryu ◽  
Joon Woo Song ◽  
Joo Hee Jeon ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Near Infrared ◽  
Mannose Receptor ◽  
Raw264.7 Cells ◽  
Plaque Burden ◽  
Glycol Chitosan ◽  
Fibrous Cap ◽  
Ppar Γ ◽  
Regulator Genes ◽  
Mannose Receptors

Introduction: Atherosclerosis is a process of lipid accumulation and inflammation. In particular, plaque macrophages are associated with fibrous cap destabilization and rupture. We hypothesized that the specific delivery of a PPAR-γ agonist to inflamed plaques via nanoprobe (NP) targeting macrophage mannose receptors could reduce plaque burden and inflammation. Methods and Results: Macrophage mannose receptor targetable nanoprobe (MMR-NP) was fabricated by chemically conjugating thiolated glycol chitosan with mannose-PEG-maleimide, followed by incorporating PPAR-γ agonist (lobeglitazone) into this nanoscale delivery system (MMR-Lobe). For in vivo monitoring of therapeutic response, near-infrared fluorescence NP was prepared by conjugation of Cy5.5 (ext/emi 675/694 nm) with MMR-NP. In cellular uptake study, the MMR-NP showed high affinity to mannose receptors on macrophages. MMR-Lobe attenuated LPS-induced inflammatory cytokines such as TNF-α, IL-6, and MMP-9 in RAW264.7 cells. Additionally, MMR-Lobe increased expression of ABCA1, ABCG1 and LXR-α, known as PPAR-γ regulator genes involved in cholesterol efflux, in RAW264.7 cells. Using a customized high-resolution intravital fluorescence microscope, the in vivo serial imaging of carotid atheroma in apoE-/- mice injected with MMR-Lobe (7 mg/kg, twice weekly for 4 weeks) revealed a significant decrease in plaque burden and inflammation (Figure) as compared to baseline, or non-treated controls, or p.o. Lobe treated mice (p<0.01 respectively, 6 mice in each group). En face imaging, FM, and immunostainings corroborated the in vivo findings. Conclusions: MMR-Lobe was able to selectively target atheroma macrophages, and effectively reduce both plaque burden and inflammation as assessed by serial intravital optical imaging. We suggest that nanoprobe-mediated PPAR-γ agonist delivery targeting plaque macrophages holds a promising theranostic approach for high-risk atheromata.

Abstract 4: Enhancing the Ability of Macrophages to Orchestrate Selective Autophagy and Lysosomal Biogenesis Protects Against Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ismail Sergin ◽  
Somashubhra Bhattacharya ◽  
Xiangyu Zhang ◽  
Trent D Evans ◽  
Babak Dehestani ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Membrane Integrity ◽  
Protein Aggregates ◽  
Plaque Burden ◽  
Inflammasome Activation ◽  
Lysosomal Degradation ◽  
Cytoplasmic Inclusions ◽  
Selective Autophagy ◽  
Mechanistic Basis

The autophagy-lysosome system is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. The pro-atherogenic phenotype of mice with macrophage-specific autophagy deficiency (ATG5-/-) confirm the importance of this degradation system in the pathogenesis of atherosclerosis. The mechanistic basis appears to involve a two-step process in macrophages: the development of lysosomal dysfunction/membrane integrity by atherogenic lipids followed by an inability of lysosomes to handle and degrade cargo supplied by autophagy. A prominent sequelae of such blockage is the accumulation of cytoplasmic inclusions composed of polyubiquitinated protein aggregates and organelles which are normally targeted for selective autophagy by the protein chaperone p62. In order to stimulate the degradative capacity of macrophages, we developed mice with macrophage-specific overexpression of TFEB, a master transcriptional activator of both autophagy and lysosomal biogenesis. Macrophage TFEB ameliorated several deleterious effects of atherogenic lipids, namely the blunting of inflammasome activation, enhancing cholesterol efflux, accelerating the degradation of protein aggregates, and decreasing apoptosis. In vivo, macrophage TFEB overexpression reduced both plaque burden and plaque complexity in pro-atherogenic ApoE-/- mice fed a Western diet. Interestingly, TFEB’s atheroprotective effects were not only abrogated in the background of macrophage autophagy deficiency (ATG5-/-) but also in the background of p62-deficiency (p62-/-) suggesting the critical importance of selective autophagy and degradation of p62-enriched protein aggregates. Taken together, these data support the induction of a holistic pro-degradative response in macrophages (i.e. selective autophagy followed by lysosomal degradation) as a viable therapeutic strategy in atherosclerosis.

scholarly journals Macrophage Scavenger Receptor A Promotes Tumor Progression in Murine Models of Ovarian and Pancreatic Cancer

2013 ◽  
Vol 190 (7) ◽  
pp. 3798-3805 ◽  
Author(s):  
Claudine Neyen ◽  
Annette Plüddemann ◽  
Subhankar Mukhopadhyay ◽  
Eleni Maniati ◽  
Maud Bossard ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Progression ◽  
Scavenger Receptor ◽  
Murine Models ◽  
Macrophage Scavenger Receptor ◽  
Scavenger Receptor A

Abstract 656: In Vivo Plaque Inflammation and Endothelial Permeability Independently Predict Atherosclerosis Progression: A Serial Multimodality Imaging Study

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Eric A Osborn ◽  
Giovanni J Ughi ◽  
Johan W Verjans ◽  
Edouard Gerbaud ◽  
Richard A Takx ◽  
...  
Keyword(s):  
Near Infrared ◽  
Ex Vivo ◽  
Multimodality Imaging ◽  
Endothelial Permeability ◽  
Imaging Study ◽  
Plaque Burden ◽  
Plaque Progression ◽  
Nirf Imaging ◽  
Imaging Results

Background: Atheroma inflammation impairs plaque stability and promotes plaque progression and complications. However, it is unknown how measures of plaque biology relate to changes in plaque burden, and whether plaque biology can independently predict plaque progression in coronary-sized arteries. This study evaluated the ability of intravascular near-infrared fluorescence (NIRF) biological imaging to inform experimental atheroma progression in vivo. Methods: Atherosclerosis was induced by balloon-injury in the aorta of 14 cholesterol-fed rabbits. Serial intravascular ultrasound (IVUS) and dual-modality intravascular NIRF - optical coherence tomography (OCT) imaging was performed following injection of a NIRF molecular imaging agent of plaque inflammatory protease activity (ProSense VM110; n=7), or impaired plaque endothelial permeability (indocyanine green (ICG); n=7). Plaque progression was further assessed by IVUS change in plaque burden. Regression analysis was used to evaluate the association of NIRF with plaque progression. In vivo imaging results were corroborated by ex vivo fluorescence reflectance imaging, fluorescence microscopy, and histopathology. Results: Quantitative analysis of 1,811 axial images spanning individual plaques, the change in NIRF plaque biological signals from 8 to 12 weeks strongly correlated with IVUS plaque burden from 8 to 12 weeks (ProSense VM110: r=0.774; ICG: r=0.572; p<0.0001). This finding remained significant on multivariate analysis adjusted for IVUS plaque burden, lumen area, and remodeling index (p<0.001). In additional multivariate analyses, the baseline NIRF signal at 8 weeks further predicted the magnitude of plaque progression even after adjustment for baseline plaque burden (p<0.001 for Prosense VM110; p=0.004 for ICG). Histology demonstrated NIRF agent uptake in inflamed, lipid-rich plaques. Conclusion: Plaque pathobiology and plaque burden progress in concert as assessed by translatable intravascular NIRF imaging technology. The baseline NIRF inflammation and impaired plaque permeability signals independently predict plaque progression. Integrated biological-microstructural imaging may enhance the ability to detect high-risk plaques at risk of progression.

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