In vivo nano contrast-enhanced photoacoustic imaging for dynamically lightening the molecular changes of rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most prevalent inflammatory joint disorders. Early diagnosis, accurate staging, and imaging guided treatment response of RA remain crucial clinical significances for improving treatment outcomes. In this study, we introduced endogenous melanin nanoparticles (MNPs) conjugated with Cyclic Arg-Gly-Asp (RGD) peptide (MNP-PEG-RGD) as a contrast agent for accurate photoacoustic imaging (PAI) of RA diagnosis. It was observed that the prepared nanoprobes had favorable PA sensitivity, photostability and biocompatibility. In vivo studies using RA mouse model revealed that this nanoprobe could target αvβ3 actively at 1 h post-injection, while the signal was remarkably increased in the arthritic joint which could earlier diagnose RA than conventional imaging system. It was of crucial importance to staging RA by PAI with significant difference in nanoprobes accumulation. Furthermore, we tracked the therapeutic efficacy of etanercept in RA treatment by PAI. The observed advancement of arthritis on the PAI was confirmed by histological and immunohistochemical analysis. In conclusion, this study shed light on the development of innovative multifunctional theranostic nanoplatform for both RA monitoring and treatment with a promising future in clinical translation.