Tocilizumab-Conjugated Polymer Nanoparticles for NIR-II Photoacoustic-Imaging-Guided Therapy of Rheumatoid Arthritis

Abstract

The progressive debilitating nature of rheumatoid arthritis (RA) combined with its unknown etiology and initial similarity to other inflammatory diseases makes early diagnosis a significant challenge. Early recognition and treatment of RA is essential for achieving effective therapeutic outcome. NIR-II photoacoustic (PA) molecular imaging (PMI) is emerging as a promising new strategy for effective diagnosis and treatment guidance of RA, owing to its high sensitivity and specificity at large penetration depth. Herein, an antirheumatic targeted drug tocilizumab (TCZ) is conjugated to polymer nanoparticles (PNPs) to develop the first NIR-II theranostic nanoplatform, named TCZ-PNPs, for PA-imaging-guided therapy of RA. The TCZ-PNPs are demonstrated to have strong NIR-II extinction coefficient, high photostability and excellent biocompatibility. NIR-II PMI results reveal the excellent targeting abilities of TCZ-PNPs for the effective noninvasive diagnosis of RA joint tissue with a high signal-to noise ratio (SNR) of 35.8 dB in 3D PA tomography images. Remarkably, one-month treatment and PA monitoring using TCZ-PNPs shows RA is significantly suppressed. In addition, the therapeutic evaluation of RA mice by NIR-II PMI is shown to be consistent with clinical micro-CT and histological analysis. The TCZ-PNPs-assisted NIR-II PMI provides a new strategy for RA theranostics, therapeutic monitoring and the beyond.

Keywords: photoacoustic molecular imaging; polymer nanoparticles; rheumatoid arthritis; second near infrared window; tocilizumab.