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Theranostics 2021; 11(1):164-180. doi:10.7150/thno.47841 This issue Cite

Research Paper

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications

Yi Wang^1,2*, Kang Zhang^1*, Tianhan Li¹, Ali Maruf¹, Xian Qin¹, Li Luo¹, Yuan Zhong¹, Juhui Qiu¹, Sean McGinty³, Giuseppe Pontrelli⁴, Xiaoling Liao^2✉, Wei Wu^1✉, Guixue Wang^1✉

1. Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.
2. Chongqing Key Laboratory of Nano/Micro Composite Material and Device, School of Metallurgy and Materials Engineering, Chongqing University of Science and Technology, Chongqing, 401331, China.
3. Division of Biomedical Engineering, University of Glasgow, UK.
4. Istituto per le Applicazioni del Calcolo - CNR, Via dei Taurini 19, 00185, Roma, Italy.
*These authors contributed equally to this work.

✉ Corresponding authors: E-mail: wanggxedu.cn (Guixue Wang); david2015edu.cn (Wei Wu); 2007099edu.cn (Xiaoling Liao).

Abstract

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy.

Methods: Based on macrophage “homing” into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined in vitro. Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined.

Results: The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells in vitro. In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions in vivo. After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration.

Conclusion: These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.

Keywords: macrophage membrane, biomimetic, targeted delivery, atherosclerosis, ApoE knockout mice

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