Synovitis in mice with inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced NIR fluorescence imaging using iRGD-targeted liposomes as fluorescence probes

Wu, Hao; Wu, Haohan; He, Yanni; Gan, Zhen; Xu, Zhili; Zhou, Meijun; Liu, Sai; Li, Hongmei

doi:10.2147/ijn.s155475

Cited by 18 publications

(13 citation statements)

References 31 publications

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“…Live imaging of the differentially-treated RA mice showed that the iELPs accumulated at the arthritic lesions where they were retained for more than 6 hours. Although fluorescence imaging is a reliable and convenient method for monitoring nanoparticle distribution in vivo , it has a short time window which may reduce the accuracy of image-guided therapy 33 . Finally, the iELPs were also biocompatible and showed no systemic toxicity.…”

Section: Discussionmentioning

confidence: 99%

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

et al. 2020

Theranostics

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Rheumatoid arthritis (RA), a common inflammatory disorder of the joints characterized by synovitis and pannus formation, often results in irreversible joint erosion and disability. Methotrexate (MTX) is the first-line drug against RA, but the therapeutic effects are sub-optimal due to its poor retention at the target sites and systemic side effects. Multifunctional nanoparticles are highly promising agents for minimally invasive, traceable and effective targeted therapy. Methods: This study developed iRGD peptide-functionalized echogenic liposomes (iELPs) which encapsulates MTX and indocyanine green (ICG) fluorescent probe through the thin film-hydration method. Results: The resulting iELPs showed high affinity for endothelial cells overexpressing αvβ3 integrin, favorable acoustic response and fluorescence tracking properties. Also, near-infrared (NIR) fluorescence imaging of iELPs and ultrasound-triggered drug release of MTX were proved in a mouse RA model, greatly improving the therapeutic efficacy and reducing MTX side effects. Histological assessment of the articular tissues further revealed significantly lower inflammatory cell infiltration and angiogenesis in the iELPs-treated and sonicated mice. Conclusion: Our study provides a promising nanoplatform for integrating ultrasound-controlled drug release and NIR fluorescence imaging for RA treatment.

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Section: Discussionmentioning

confidence: 99%

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

et al. 2020

Theranostics

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“…13,78,79 This is surprising since the photochemical instability of ICG has been known for long time. 14,15,80,33 We conducted a photobleaching experiment that irradiated a comparative set of ICG liposomes containing three different amounts of α-tocopherol (0, 10, or 20%) and monitored the change in the intensity of ICG absorption and fluorescence signal. The data in Figure 6 (spectral data in Figure S20) shows that ICG photobleaching was substantially attenuated when the liposomes contained 10 or 20% α-tocopherol (compositions 9′ or 10′).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…ICG is an amphiphilic molecule with a propensity to self-aggregate at low micromolar concentrations in water, and its log P has been measured to be 1.81 when the aqueous phase is phosphate buffer (100 mM, pH 7.4) . Over the years, efforts to improve the photophysical and pharmaceutical properties of ICG have investigated numerous nanoparticle formulations. − A significant fraction of these nanoparticle formulations are ICG-containing liposomes, and they have been evaluated for various applications in fluorescence imaging and phototherapeutics. ,− Quite a few published studies have assessed the stability of ICG-containing liposomes by monitoring the change in sample absorbance or fluorescence intensity over time. However, this type of bulk sample measurement does not unambiguously eliminate the possibility of ICG transfer from the liposomes to albumin and related serum proteins within the same sample.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Transfer of Indocyanine Green from Liposomes to Albumin Is Inhibited by the Antioxidant α-Tocopherol

Gamage

Smith

2022

Langmuir

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Indocyanine Green (ICG) is a clinically approved organic dye with near-infrared absorption and fluorescence. Over the years, many efforts to improve the photophysical and pharmacokinetic properties of ICG have investigated numerous nanoparticle formulations, especially liposomes with membraneembedded ICG. A series of systematic absorption and fluorescence experiments, including FRET experiments using ICG as a fluorescence energy acceptor, found that ICG transfers spontaneously from liposomes to albumin protein residing in the external solution with a half-life of ∼10 min at 37 °C. Moreover, transfer of ICG from liposome membranes to external albumin reduces lightactivated leakage from thermosensitive liposomes with membrane-embedded ICG. A survey of lipophilic liposome additives discovered that the presence of clinically approved antioxidant, α-tocopherol, greatly increases ICG retention in the liposomes (presumably by forming favorable aromatic stacking interactions), inhibits ICG photobleaching and prevents albumin-induced reduction of light-triggered liposome leakage. This new insight will help researchers with the specific task of optimizing ICGcontaining liposomes for fluorescence imaging or phototherapeutics. More broadly, the results suggest a broader design concept concerning light triggered liposome leakage, that is, proximity of the light absorbing dye to the bilayer membrane is a critical design feature that impacts the extent of liposome leakage.

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“…Previous reports indicate that Near-infrared fluorescence imaging system with ICG show significant accumulation in inflamed joints with enhanced permeability and retention (EPR), like as the accumulation observed in tumors [29, 30]. Blood vessel insufficiency of inflamed joints in arthritic experimental models increases the leakiness and permeability, which enhances the accumulation of liposomes in arthritic lesion by EPR [31].…”

Section: Methodsmentioning

confidence: 99%

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis

Izumiyama

Mori

et al. 2019

BMC Musculoskelet Disord

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Background McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16–1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. Methods Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16–1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. Results Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16–1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16–1 treated groups. Conclusions Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.

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Synovitis in mice with inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced NIR fluorescence imaging using iRGD-targeted liposomes as fluorescence probes

Cited by 18 publications

References 31 publications

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheumatoid Arthritis by MTX-ICG-loaded iRGD-modified echogenic liposomes

Spontaneous Transfer of Indocyanine Green from Liposomes to Albumin Is Inhibited by the Antioxidant α-Tocopherol

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis

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