Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway

Wenming He; Shuangshuang Tu; Jinru Han; Haijing Cui; Liangxue Lai; Yonglong Ye; Ting Dai; Yannan Yuan; Lili Ji; Jiayong Luo; Wenzhi Ren; Aiguo Wu

doi:10.1016/j.actbio.2024.05.009

Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway

Acta Biomater. 2024 May 9:S1742-7061(24)00252-6. doi: 10.1016/j.actbio.2024.05.009. Online ahead of print.

Authors

Wenming He¹, Shuangshuang Tu¹, Jinru Han², Haijing Cui³, Liangxue Lai³, Yonglong Ye³, Ting Dai¹, Yannan Yuan¹, Lili Ji¹, Jiayong Luo¹, Wenzhi Ren⁴, Aiguo Wu⁵

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, 315020, China.
² Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
³ Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.
⁴ Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China; Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China. Electronic address: renwzh@nimte.ac.cn.
⁵ Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China; Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China. Electronic address: aiguo@nimte.ac.cn.

PMID: 38734283
DOI: 10.1016/j.actbio.2024.05.009

Abstract

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.

Keywords: Atherosclerosis; Lipid metabolism; Macrophage polarization; Nanomicelles; Phototherapy.