4.8 Article

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications

Journal

THERANOSTICS
Volume 11, Issue 1, Pages 164-180

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.47841

Keywords

macrophage membrane; biomimetic; targeted delivery; atherosclerosis; ApoE knockout mice

Funding

  1. National Natural Science Foundation of China [31971301, 31971242, 12032007]
  2. China Postdoctoral Science Foundation [2020M673143]
  3. Natural Science Foundation of Chongqing [cstc2020jcyj-bsh0025, cstc2019jcyj-zdxm X0028, cstc2017jcyjAX0186]
  4. Fundamental Research Funds for Central Universities [2020CDJQY-A061, 2019CDYGZD008, 2018CDHB1B08]
  5. National 111 Project Base [B0625]

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This study aimed to develop an ideal biomimetic nanoparticle for targeted atherosclerosis (AS) therapy. The results showed that the advanced MM/RAPNPs demonstrated good biocompatibility, effectively inhibited the progression of AS, and displayed favorable safety performance in AS mouse models. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.
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.

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