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

Abstract

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.

Application of nanomaterials in the treatment of rheumatoid arthritis

“…Wu et al 48 prepared iRGD peptide-functionalized echogenic liposomes (iELPs) encapsulated MTX, which contained indocyanine green (ICG) fluorescent probes for fluorescence tracking, and the drug release was triggered by low-frequency ultrasound. In RA mice, iELPs can bind to the αvβ3 integrin in the synovium, which greatly improves the therapeutic effect.…”

“…The schematic illustration of iELPs and the mechanism of NIR fluorescence imaging and treatment 48. Adapted with permission from ref.…”

Liposomal Nanosystems in Rheumatoid Arthritis

“…In iRGD active targeting, the combination of echogenic liposomes (PDI: 0.2, ζ: −6 to −14 mV, E.E. : 69%) and ultrasounds were explored, resulting in dexamethasone release from liposomes induced by low-frequency ultrasounds [ 103 ]. In this study, a higher therapeutic effect was obtained when liposomes and ultrasounds were combined as a therapy, in comparison with all the other groups—free drug, targeted liposomes without ultrasounds and non-targeted liposomes with ultrasounds.…”

Recent Advances in Liposomal-Based Anti-Inflammatory Therapy

“…The overview in Table 1 provides a summary of innovative research conducted in this field. Recent notable innovations include liposomal drugs where liposomes are modified for local accumulation via peptide binding or folate conjugation or modified for local release through reactivity to pH, ultrasound, or thermosensitivity [ 85 , 86 , 87 , 88 ]. Additionally, conventional drugs are combined and encapsulated in liposomes to enable codelivery in order to evaluate a potential synergistic effect [ 89 , 90 , 91 , 92 ].…”