A major obstacle in osteoarthritis (OA) theranostics is the lack of a timely and accurate monitoring method. It is hypothesized that the loss of anionic glycosaminoglycans (GAGs) in articular cartilage reflects the progression of OA. Thus, this study investigated the feasibility of photoacoustic imaging (PAI) applied for monitoring the in vivo course of OA progression via GAG-targeted cationic nanoprobes. The nanoprobes were synthesized through electrostatic attraction between poly-L-Lysine and melanin (PLL-MNPs). Cartilage explants with different concentrations of GAGs incubated with PLL-MNPs to test the relationship between GAGs content and PA signal intensity. GAG activity was then evaluated in vivo in destabilization of the medial meniscus (DMM) surgically-induced mouse model. To track OA progression over time, mice were imaged consistently for 10 weeks after OA-inducing surgery. X-ray was used to verify the superiority of PAI in detecting OA. The correlation between PAI data and histologic results was also analyzed. In vitro study demonstrated the ability of PLL-MNPs in sensitively detecting different GAGs concentrations. In vivo PAI exhibited significantly lower signal intensity from OA knees compared to normal knees. More importantly, PA signal intensity showed serial reduction over the course of OA, while X-ray showed visible joint destruction until 6 weeks. A decrease in GAGs content was confirmed by histologic examinations; moreover, histologic findings were well correlated with PAI results. Therefore, using cationic nanoprobe-enhanced PAI to detect the changes in GAG contents provides sensitive and consistent visualization of OA development. This approach will further facilitate OA theranostics and clinical translation.Copyright © 2020. Published by Elsevier Ltd.
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