Platelet membrane-coated nanoparticle-mediated targeting delivery of Rapamycin blocks atherosclerotic plaque development and stabilizes plaque in apolipoprotein E-deficient (ApoE−/−) mice

• Published in: Nanomedicine Vol. 15; no. 1; pp. 13 - 24
• Main Authors: Song, Yanan, Huang, Zheyong, Liu, Xin, Pang, Zhiqing, Chen, Jing, Yang, Hongbo, Zhang, Ning, Cao, Zhonglian, Liu, Ming, Cao, Jiatian, Li, Chenguang, Yang, Xiangdong, Gong, Hui, Qian, Juying, Ge, Junbo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019
• Subjects: Animals; Apolipoproteins E - genetics; Apolipoproteins E - physiology; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - genetics; Atherosclerosis - pathology; Autophagy; Blood Platelets - physiology; Cell Membrane - chemistry; Cell Membrane - metabolism; Cells, Cultured; Drug Delivery Systems; Immunosuppressive Agents - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Plaque, Atherosclerotic - drug therapy; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - pathology; Platelet Adhesiveness; Platelet membrane-coated nanoparticle; Rapamycin; Sirolimus - pharmacology; Targeting delivery; RAP; vWF; PT; ALT; DLS; Targeting delivery; SMCs; Autophagy; HDL; Platelet membrane-coated nanoparticle; PNP; LDL; CM-NP; Atherosclerosis; BUN; ApoE−/− mice; RAP-PNP; AST; RAP-NP; Rapamycin; TC; APTT; PLGA; TG; TEM; DiD; HUVECs
• ISSN: 1549-9634; 1549-9642; 1549-9642
• DOI: 10.1016/j.nano.2018.08.002

Although certain success has been achieved in atherosclerosis treatment, tremendous challenges remain in developing more efficient strategies to treat atherosclerosis. Platelets have inherent affinity to plaques and naturally home to atherosclerotic sites. Rapamycin features potent anti-atherosclerosis effect, but its clinical utility is limited by its low concentration at the atherosclerotic site and severe systemic toxicity. In the present study, we used platelet membrane-coated nanoparticles (PNP) as a targeted drug delivery platform to treat atherosclerosis through mimicking platelets' inherent targeting to plaques. PNP displayed 4.98-fold greater radiant efficiency than control nanoparticles in atherosclerotic arterial trees, indicating its effective homing to atherosclerotic plaques in vivo. In an atherosclerosis model established in apolipoprotein E-deficient mice, PNP encapsulating rapamycin significantly attenuated the progression of atherosclerosis and stabilized atherosclerotic plaques. These results demonstrated the perfect efficacy and pro-resolving potential of PNP as a targeted drug delivery platform for atherosclerosis treatment. Platelet membranes were coated onto the surface of PLGA cores to mimic platelet inherent affinity to atherosclerotic plaques. TEM showed most PNP were well coated with platelet membranes. PNP could effectively target atherosclerotic plaques, delayed the progression of atherosclerosis and stabilized atherosclerotic plaques when encapsulating RAP, representing a promising platform for the treatment of atherosclerosis. [Display omitted]