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Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near\u2010infrared fluorescence (NIR\u2010II FL)\/photoacoustic (PA) dual\u2010model imaging\u2010guided multi\u2010treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin\u2010nanoparticles (MNPs), hydrogen gas (H\n                    <jats:sub>2<\/jats:sub>\n                    ), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H\n                    <jats:sub>2<\/jats:sub>\n                    exhibits precise synergistic antioxidant and anti\u2010inflammatory effects with MNPs. Moreover, the ICG, the second near\u2010infrared dye currently approved for clinical use, possesses excellent NIR\u2010II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time\u2010point for PTT.\n                  <\/jats:p>","DOI":"10.1002\/advs.202401046","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T05:39:43Z","timestamp":1714109983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endogenous Melanin and Hydrogen\u2010Based Specific Activated Theranostics Nanoagents: A Novel Multi\u2010Treatment Paradigm for Rheumatoid Arthritis"],"prefix":"10.1002","volume":"11","author":[{"given":"Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital)  Taiyuan 030000 China"},{"name":"Academy of Medical Sciences Shanxi 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