A Mesoporous Silica-Based Naringenin Delivery System Promoting Macrophage M2 Polarization in Atherosclerosis
A Mesoporous Silica-Based Naringenin Delivery System Promoting Macrophage M2 Polarization in Atherosclerosis
Shenhui Ren(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Junchao Liu(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Hongji Pu(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Penghui Wang(Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University); Xiaodong Wu(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Jinbao Qin(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Xiaobing Liu(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Minyi Yin(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Xinwu Lu(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Bo Li(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine); Zhen Zhao(Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine)
29권, 1928~1943쪽
초록
Atherosclerosis is the leading cause of global cardiovascular morbidity and mortality associated with inflammatory and immunological mechanisms. Immunotherapy has demonstrated promising efficacy in the management of atherosclerosis. Nevertheless, certain immunotherapeutic approaches are associated with limitations, including suboptimal efficacy and non-negligible adverse effects. Upon the pivotal role of macrophage phenotypes in atherosclerosis progression, naringenin-loaded manganese-doped mesoporous silica nanoparticles (MMSN@NAR) were designed and synthesized to reprogram M1 macrophages toward the M2 phenotype, thereby offering a potential therapeutic strategy for atherosclerosis treatment. High loading capacity of naringenin was achieved in MMSN carriers, with superior biocompatibility profiles compared to naringenin dissolved in dimethyl sulfoxide, while maintaining pH-dependent release behavior as demonstrated by dialysis assays. MMSN@NAR is preferentially phagocytosed by M1 macrophages, attenuates inflammatory responses, protects against oxidative stress, and promotes M2 polarization via the AMP-activated protein kinase (AMPK) pathway in vitro. Atherosclerosis is the leading cause of global cardiovascular morbidity and mortality associated with inflammatory and immunological mechanisms. Immunotherapy has demonstrated promising efficacy in the management of atherosclerosis. Nevertheless, certain immunotherapeutic approaches are associated with limitations, including suboptimal efficacy and non-negligible adverse effects. Upon the pivotal role of macrophage phenotypes in atherosclerosis progression, naringenin-loaded manganese-doped mesoporous silica nanoparticles (MMSN@NAR) were designed and synthesized to reprogram M1 macrophages toward the M2 phenotype, thereby offering a potential therapeutic strategy for atherosclerosis treatment. High loading capacity of naringenin was achieved in MMSN carriers, with superior biocompatibility profiles compared to naringenin dissolved in dimethyl sulfoxide, while maintaining pH-dependent release behavior as demonstrated by dialysis assays. MMSN@NAR is preferentially phagocytosed by M1 macrophages, attenuates inflammatory responses, protects against oxidative stress, and promotes M2 polarization via the AMP-activated protein kinase (AMPK) pathway in vitro. In the ApoE-/- mouse unilateral carotid artery ligation model of atherosclerosis, MMSN@NAR demonstrated marked accumulation in plaques and excellent biocompatibility. Compared to using naringenin or MMSN alone, it could further reduce plaque area by approximately 40% or 60% by inducing macrophage phenotype transformation, which was confirmed by section staining and immunofluorescence. Collectively, this study highlights enhanced macrophage M2 polarization inhibiting atherosclerosis by MMSN@NAR as a promising nanoplatform, offering a novel therapeutic approach based on anti-inflammatory immune regulation.
Abstract
Atherosclerosis is the leading cause of global cardiovascular morbidity and mortality associated with inflammatory and immunological mechanisms. Immunotherapy has demonstrated promising efficacy in the management of atherosclerosis. Nevertheless, certain immunotherapeutic approaches are associated with limitations, including suboptimal efficacy and non-negligible adverse effects. Upon the pivotal role of macrophage phenotypes in atherosclerosis progression, naringenin-loaded manganese-doped mesoporous silica nanoparticles (MMSN@NAR) were designed and synthesized to reprogram M1 macrophages toward the M2 phenotype, thereby offering a potential therapeutic strategy for atherosclerosis treatment. High loading capacity of naringenin was achieved in MMSN carriers, with superior biocompatibility profiles compared to naringenin dissolved in dimethyl sulfoxide, while maintaining pH-dependent release behavior as demonstrated by dialysis assays. MMSN@NAR is preferentially phagocytosed by M1 macrophages, attenuates inflammatory responses, protects against oxidative stress, and promotes M2 polarization via the AMP-activated protein kinase (AMPK) pathway in vitro. Atherosclerosis is the leading cause of global cardiovascular morbidity and mortality associated with inflammatory and immunological mechanisms. Immunotherapy has demonstrated promising efficacy in the management of atherosclerosis. Nevertheless, certain immunotherapeutic approaches are associated with limitations, including suboptimal efficacy and non-negligible adverse effects. Upon the pivotal role of macrophage phenotypes in atherosclerosis progression, naringenin-loaded manganese-doped mesoporous silica nanoparticles (MMSN@NAR) were designed and synthesized to reprogram M1 macrophages toward the M2 phenotype, thereby offering a potential therapeutic strategy for atherosclerosis treatment. High loading capacity of naringenin was achieved in MMSN carriers, with superior biocompatibility profiles compared to naringenin dissolved in dimethyl sulfoxide, while maintaining pH-dependent release behavior as demonstrated by dialysis assays. MMSN@NAR is preferentially phagocytosed by M1 macrophages, attenuates inflammatory responses, protects against oxidative stress, and promotes M2 polarization via the AMP-activated protein kinase (AMPK) pathway in vitro. In the ApoE-/- mouse unilateral carotid artery ligation model of atherosclerosis, MMSN@NAR demonstrated marked accumulation in plaques and excellent biocompatibility. Compared to using naringenin or MMSN alone, it could further reduce plaque area by approximately 40% or 60% by inducing macrophage phenotype transformation, which was confirmed by section staining and immunofluorescence. Collectively, this study highlights enhanced macrophage M2 polarization inhibiting atherosclerosis by MMSN@NAR as a promising nanoplatform, offering a novel therapeutic approach based on anti-inflammatory immune regulation.
- 발행기관:
- 한국생체재료학회
- 분류:
- 의공학