Universal cell membrane camouflaged nano-prodrugs with right-side-out orientation adapting for positive pathological vascular remodeling in atherosclerosis

A right-side-out orientated self-assembly of cell membrane-camouflaged nanotherapeutics is crucial for ensuring their biological functionality inherited from the source cells. In this study, a universal and spontaneous right-side-out coupling-driven ROS-responsive nanotherapeutic approach, based on...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2024-05, Vol.15 (2), p.7524-7544
Main Authors: Qin, Xian, Zhu, Li, Zhong, Yuan, Wang, Yi, Luo, Xiaoshan, Li, Jiawei, Yan, Fei, Wu, Guicheng, Qiu, Juhui, Wang, Guixue, Qu, Kai, Zhang, Kun, Wu, Wei
Format: Article
Language:English
Subjects:
Atherosclerosis
Bioengineering
Biomedical materials
Cell membranes
Chemistry
Drugs
Efflux
Lipids
Self-assembly
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Summary:A right-side-out orientated self-assembly of cell membrane-camouflaged nanotherapeutics is crucial for ensuring their biological functionality inherited from the source cells. In this study, a universal and spontaneous right-side-out coupling-driven ROS-responsive nanotherapeutic approach, based on the intrinsic affinity between phosphatidylserine (PS) on the inner leaflet and PS-targeted peptide modified nanoparticles, has been developed to target foam cells in atherosclerotic plaques. Considering the increased osteopontin (OPN) secretion from foam cells in plaques, a bioengineered cell membrane (OEM) with an overexpression of integrin α9β1 is integrated with ROS-cleavable prodrugs, OEM-coated ETBNPs (OEM-ETBNPs), to enhance targeted drug delivery and on-demand drug release in the local lesion of atherosclerosis. Both in vitro and in vivo experimental results confirm that OEM-ETBNPs are able to inhibit cellular lipid uptake and simultaneously promote intracellular lipid efflux, regulating the positive cellular phenotypic conversion. This finding offers a versatile platform for the biomedical applications of universal cell membrane camouflaging biomimetic nanotechnology. The preparation of right-side-out-orientated coupling-driven ROS-sensitive nanoparticles on the inner leaflet of the cell membrane for positively regulating cell phenotypic conversion in atherosclerosis.
ISSN:2041-6520
2041-6539
DOI:10.1039/d4sc00761a