Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.

中文翻译：

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基于聚合网络的人工过氧化物酶体重编程巨噬细胞用于光声成像引导治疗类风湿关节炎


具有模拟酶催化活性和募集能力的人工过氧化物酶体（AP）在构建用于清除活性氧（ROS）、调节炎症微环境和重编程巨噬细胞的原细胞系统方面引起了广泛关注，在治疗疾病方面具有巨大潜力炎症性疾病，例如类风湿性关节炎（RA）。在此，制备了一种巨噬细胞膜包裹的铜配位聚酞菁基AP（CuAP），具有大环共轭聚合网络和嵌入的铜单原子活性中心，模拟天然超氧化物歧化酶和过氧化氢酶的催化活性和配位环境，具有巨噬细胞的炎症募集能力，并进行光声成像（PAI）引导的治疗。体外细胞和体内动物实验结果表明，超声和微泡作用下的CuAP可以有效清除细胞和组织中过量的ROS，调节微环境炎症细胞因子，如白介素-1β、肿瘤坏死因子-α和精氨酸酶-1 ，并通过 M1（促炎表型）极化至 M2（抗炎表型）来重新编程巨噬细胞。我们相信这项研究为设计多方面的 AP 提供了概念验证，并为 PAI 引导的 RA 治疗平台提供了一种有前途的方法。