Biomimetic nanoparticles loaded lutein functionalized by macrophage membrane for targeted amelioration pressure overload-induced cardiac fibrosis

作者全名："Guo, Tingting; Chen, Lihua; Li, Fang; Cao, Yang; Li, Dan; Xiong, Qingsong; Ling, Zhiyu"

作者地址："[Guo, Tingting; Chen, Lihua; Li, Fang; Li, Dan; Xiong, Qingsong; Ling, Zhiyu] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Cao, Yang] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Inst Ultrasound Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Ling, ZY (通讯作者)，Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001097328200001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：167

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Cardiac fibrosis; Biomimetic nanoparticles; Lutein; Targeting delivery; IL-11

摘要："Lutein is a strong antioxidant with anti-inflammatory, anti-oxidative and cardioprotective effects and could be a promising candidate for the treatment of hypertensive heart disease (HHD), but is not clinically appealing because of its low oral bioavailability and main distribution in the eyes. To address this, a biomimetic drug delivery system-MMLNPs was established by coating macrophage membranes (MMs) onto lutein-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (LNPs). This study characterized the physical properties of biomimetic nanoparticles and examined the targeting capability, therapeutic effects and mechanism, and biosecurity of administering them for cardiac fibrosis therapy in the transverse aortic constriction (TAC) model and in vitro. Transmission electron microscope mapping and dynamic light scattering analysis proved that MMLNPs were spherical nanoparticles camouflaged by a layer of cell membrane and had negative zeta potential. Confocal laser scanning microscopy and flow cytometry analysis showed that MMs on the biomimetic nanoparticles hindered the phagocytosis of macrophages and facilitated the targeting of activated endothelial cells. Ex vivo fluorescence imaging experiments demonstrated the targeting of biomimetic nanoparticles to the injured heart. EdU assay indicated that MMLNPs have the same potential to inhibit angiotensin (Ang) II-induced cardiac fibroblast proliferation as free lutein. Furthermore, echocardiography showed that MMLNPs improved cardiac function and structure, and Masson staining and western blotting showed that MMLNPs ameliorated cardiac fibrosis. We found MMLNPs inhibited the interleukin (IL)-11/ERK signaling pathway which was up-regulated in the TAC model compared to the sham-operated mouse. Biochemical testing and hematoxylin and eosin staining proved that the long-term use of MMLNPs lacked biological toxicity. Collectively, MMLNPs might be a promising nanodrug delivery approach to attenuate pressure overload (PO)-induced cardiac fibrosis."

基金机构："National Natural Science Foundation of China [82170520]; Natural Science Foundation Project of Chongqing [cstc2021jcyj-msxmX0075]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0078]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China [(2020)7]"

基金资助正文："This research is funded by the National Natural Science Foundation of China (Grant number 82170520), Natural Science Foundation Project of Chongqing (cstc2021jcyj-msxmX0075), Program for Youth Innovation in Future Medicine, Chongqing Medical University (Grant number W0078), and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (grant number (2020)7). However, the funding agencies had no influence on study design, study performance, data collection, data analysis, data interpretation, and manuscript preparation."