Inflammation-Responsive Nanoagents for Activatable Photoacoustic Molecular Imaging and Tandem Therapies in Rheumatoid Arthritis

促炎细胞因子 炎症 材料科学 类风湿性关节炎 生物医学中的光声成像 生物物理学 医学 免疫学 生物 物理 光学
作者
Yuan Zhang,Xiaoying Kang,Jia Li,Jianwen Song,Xueping Li,Wen Li,Ji Qi
出处
期刊:ACS Nano [American Chemical Society]
卷期号:18 (3): 2231-2249 被引量:23
标识
DOI:10.1021/acsnano.3c09870
摘要

Rheumatoid arthritis (RA) severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, representing a pressing public health concern. The pathogenesis of RA includes the excessive production of proinflammatory cytokines and harmful oxygen-derived free radicals, such as nitric oxide (NO), which constitute vital targets for precise diagnosis and effective treatment of RA. In this study, we introduce an advanced nanoagent that integrates the RA microenvironment-activatable photoacoustic (PA) imaging with multitarget synergistic treatment for RA. A highly sensitive organic probe with NO-tunable energy transformation and molecular geometry is developed, which enables strong near-infrared absorption with a turn-on PA signal, and the active intramolecular motion could further boost PA conversion. The probe is coassembled with an inflammation-responsive prodrug to construct the theranostic nanoagent, on which a macrophage-derived cell membrane with natural tropism to the inflammatory sites is camouflaged to improve the targeting ability to inflamed joints. The nanoagent could not only sensitively detect RA and differentiate the severity but also efficiently alleviate RA symptoms and improve joint function. The combination of activatable probe-mediated NO scavenging and on-demand activation of anti-inflammatory prodrug significantly inhibits the proinflammatory factors and promotes macrophage repolarization from M1 to M2 phenotype. This meticulously designed nanoagent ingeniously integrates RA-specific PA molecular imaging with synergistic multitarget therapy, rendering tremendous promise for precise intervention of RA-related diseases.
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