Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice

Abstract Atherosclerosis (AS), a leading contributor to global cardiovascular mortality, is primarily driven by the dual pathological processes of chronic persistent inflammation and dysregulated lipid metabolism. Current clinical interventions are predominantly limited to single-target approaches (...

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Main Authors: Yi Liu, Shengchao Ma, Feng Li, Hanshuang Ding, Qi Zhang, Feifei Yu, Huiping Zhang, Yinju Hao, Bin Liu, Yideng Jiang
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03444-5
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author Yi Liu
Shengchao Ma
Feng Li
Hanshuang Ding
Qi Zhang
Feifei Yu
Huiping Zhang
Yinju Hao
Bin Liu
Yideng Jiang
author_facet Yi Liu
Shengchao Ma
Feng Li
Hanshuang Ding
Qi Zhang
Feifei Yu
Huiping Zhang
Yinju Hao
Bin Liu
Yideng Jiang
author_sort Yi Liu
collection DOAJ
description Abstract Atherosclerosis (AS), a leading contributor to global cardiovascular mortality, is primarily driven by the dual pathological processes of chronic persistent inflammation and dysregulated lipid metabolism. Current clinical interventions are predominantly limited to single-target approaches (e.g., lipid-lowering therapies), which are insufficient for simultaneously modulating the two pathophysiological mechanisms and inhibiting atherosclerotic progression. Recently, combination therapeutic strategies based on multi-target and multi-organ synergistic effects have gained increasing attention in AS treatment. In this study, we developed a dual-functional nanodelivery system co-encapsulating PCSK9 inhibitor of evolocumab and natural anti-inflammatory agent of curcumin, with surface modification using macrophage membranes (Møm) and hyaluronic acid (HA). This novel design not only confers immune evasion capability to the nanocomplex but also facilitates drug accumulation in atherosclerotic lesions and hepatic tissues, thereby enabling synchronous regulation of the inflammatory microenvironment and lipid metabolic homeostasis. In vivo studies demonstrated remarkable therapeutic efficacy of this nanoformulation on atherosclerosis by effectively reducing plaque area, enhancing plaque stability and markedly ameliorating hepatic lipid accumulation. Overall, the proposed strategy, which enables multi-target and multi-organ synergistic regulation of inflammatory responses and lipid metabolism disorder, provides a promising approach for the clinical management of atherosclerosis.
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issn 1477-3155
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series Journal of Nanobiotechnology
spelling doaj-art-82e05f329c324da384d140fe72b3aef72025-08-20T03:46:27ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112310.1186/s12951-025-03444-5Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− miceYi Liu0Shengchao Ma1Feng Li2Hanshuang Ding3Qi Zhang4Feifei Yu5Huiping Zhang6Yinju Hao7Bin Liu8Yideng Jiang9Department of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical UniversityGeneral Hospital of Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical UniversityGeneral Hospital of Ningxia Medical UniversityNHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Ningxia Medical UniversityAbstract Atherosclerosis (AS), a leading contributor to global cardiovascular mortality, is primarily driven by the dual pathological processes of chronic persistent inflammation and dysregulated lipid metabolism. Current clinical interventions are predominantly limited to single-target approaches (e.g., lipid-lowering therapies), which are insufficient for simultaneously modulating the two pathophysiological mechanisms and inhibiting atherosclerotic progression. Recently, combination therapeutic strategies based on multi-target and multi-organ synergistic effects have gained increasing attention in AS treatment. In this study, we developed a dual-functional nanodelivery system co-encapsulating PCSK9 inhibitor of evolocumab and natural anti-inflammatory agent of curcumin, with surface modification using macrophage membranes (Møm) and hyaluronic acid (HA). This novel design not only confers immune evasion capability to the nanocomplex but also facilitates drug accumulation in atherosclerotic lesions and hepatic tissues, thereby enabling synchronous regulation of the inflammatory microenvironment and lipid metabolic homeostasis. In vivo studies demonstrated remarkable therapeutic efficacy of this nanoformulation on atherosclerosis by effectively reducing plaque area, enhancing plaque stability and markedly ameliorating hepatic lipid accumulation. Overall, the proposed strategy, which enables multi-target and multi-organ synergistic regulation of inflammatory responses and lipid metabolism disorder, provides a promising approach for the clinical management of atherosclerosis.https://doi.org/10.1186/s12951-025-03444-5AtherosclerosisInflammationLipid metabolismNanodelivery systemEvolocumabCurcumin
spellingShingle Yi Liu
Shengchao Ma
Feng Li
Hanshuang Ding
Qi Zhang
Feifei Yu
Huiping Zhang
Yinju Hao
Bin Liu
Yideng Jiang
Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
Journal of Nanobiotechnology
Atherosclerosis
Inflammation
Lipid metabolism
Nanodelivery system
Evolocumab
Curcumin
title Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
title_full Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
title_fullStr Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
title_full_unstemmed Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
title_short Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoE−/− mice
title_sort biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti atherosclerosis therapy in apoe mice
topic Atherosclerosis
Inflammation
Lipid metabolism
Nanodelivery system
Evolocumab
Curcumin
url https://doi.org/10.1186/s12951-025-03444-5
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