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.
基金:
National Natural Science Foundation of China [81573047, 81502367, 81702712]; Fundamental Research Funds for the Central Universities [HUST: 2018JYCXJJ018]; Natural Science Foundation of Hubei Scientific Committee [2018CFB600]
第一作者单位:[1]Huazhong Univ Sci & Technol, Union Hosp, Dept Dermatol, Tongji Med Coll, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Xu Nan,Li Jun,Gao Yujie,et al.Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus[J].BIOMATERIALS.2019,197:380-392.doi:10.1016/j.biomaterials.2019.01.034.
APA:
Xu, Nan,Li, Jun,Gao, Yujie,Zhou, Nuoya,Ma, Qiuying...&Tao, Juan.(2019).Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus.BIOMATERIALS,197,
MLA:
Xu, Nan,et al."Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus".BIOMATERIALS 197.(2019):380-392