Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus
Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus
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负载LXR激动剂的模拟凋亡细胞金纳米笼可减轻小鼠系统性红斑狼疮的进展
DOI：
10.1016/j.biomaterials.2019.01.034
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Tao Juan
中科院分区：
文献类型：
--
作者：
Xu Nan;Li Jun;Gao Yujie;Zhou Nuoya;Ma Qiuying;Wu Min;Zhang Yamin;Sun Xiaoyan;Xie Jun;Shen Guanxin;Yang Ming;Tu Qiming;Xu Xiaowei;Zhu Jintao;Tao Juan
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是对自身抗原的耐受性破坏，持续产生致病性自身抗体，并损害多个器官和组织。基于纳米颗粒（NP）的治疗剂已经证明在减缓SLE进展方面的功效。然而，针对SLE发病机制中关键起始因素的纳米药物的研究，例如，吞噬细胞对凋亡细胞的无效清除以及随之而来的自身抗原的积累很少有报道。在这里，凋亡细胞模拟金纳米笼（AuNC）的纳米药物载体，能够纠正SLE中凋亡细胞的清除受损的合理设计和产生的脂质体包被的AuNC表面上的磷脂酰丝氨酸（PS）的肝X受体（LXR）激动剂T0901317交付。值得注意的是，PS-脂质体-AuNC@T0901317可以通过提高Mer（巨噬细胞上的关键吞噬相关受体之一）的表达来有效地增强凋亡细胞清除，从而导致狼疮模型小鼠中抗dsDNA自身抗体的产生减少、炎症反应减少和肾损伤减轻。此外，PS-脂质体-AuNC可以通过光声成像跟踪纳米药物载体的生物分布。通过解决SLE的关键致病因素，在这项研究中，基于NP的递送系统被设想为治疗这种复杂且具有挑战性的疾病提供有希望的策略。
Systemic lupus erythematosus (SLE) constitutes an autoimmune disease characterized by the breakdown of tolerance to self-antigens, sustained production of pathogenic autoantibodies, and damage to multiple organs and tissues. Nanoparticle (NP)-based therapeutics have demonstrated efficacy in attenuating the progression of SLE. However, investigations of nano-drugs that address the crucial initiating factor in the pathogenesis of SLE; e.g., inefficient clearance of apoptotic cells by phagocytes and consequent accumulation of self-antigens, have seldom been reported. Here, an apoptotic cell-mimicking gold nanocage (AuNC)-based nano drug carrier capable of correcting the impaired clearance of apoptotic cells in SLE was rationally designed and generated by conjugating phosphatidylserine (PS) on the surface of liposome-coated AuNCs for liver X receptor (LXR) agonist T0901317 delivery. Notably, PS-lipos-AuNC@T0901317 could efficiently enhance apoptotic cell clearance by elevating the expression of Mer, one of the pivotal phagocytosis-associated receptors on macrophages, resulting in decreased production of anti-dsDNA autoantibodies, reduced inflammatory response, and alleviation of kidney damage in lupus model mice. Additionally, PS-lipos-AuNC could be tracked by photoacoustic imaging for nano drug carrier biodistribution. By addressing the crucial pathogenic factor of SLE, the NP-based delivery system in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.