Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin

Abstract Early identification and treatment of ventricular remodeling (VR) are crucial for delaying the progression of heart failure after myocardial infarction. This study aims to develop a dual-responsive phase-shift molecular probe loaded with a cholecystokinin octapeptide (CCK-8) and oxygen, whi...

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Main Authors: Can Wang, Hongfeng Cheng, Xiaoying Dong, Yue Zhan, Ying Liu, Nianhong Wu, Rui Tang, Hongye He, Yuting Cao, Liping Yang, Jianli Ren, Xingsheng Li, Pan Li
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03183-7
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author Can Wang
Hongfeng Cheng
Xiaoying Dong
Yue Zhan
Ying Liu
Nianhong Wu
Rui Tang
Hongye He
Yuting Cao
Liping Yang
Jianli Ren
Xingsheng Li
Pan Li
author_facet Can Wang
Hongfeng Cheng
Xiaoying Dong
Yue Zhan
Ying Liu
Nianhong Wu
Rui Tang
Hongye He
Yuting Cao
Liping Yang
Jianli Ren
Xingsheng Li
Pan Li
author_sort Can Wang
collection DOAJ
description Abstract Early identification and treatment of ventricular remodeling (VR) are crucial for delaying the progression of heart failure after myocardial infarction. This study aims to develop a dual-responsive phase-shift molecular probe loaded with a cholecystokinin octapeptide (CCK-8) and oxygen, which will provide a new integrated scheme for the assessment and treatment of VR. Biocompatible phospholipid shells were utilized to encapsulate CCK-8 and perfluoropentane (PFP), an efficient oxygen carrier. Surface modification involves reactive oxygen species (ROS)-responsive thioketal (TK) bonds and anti-ICAM-1 antibodies to create CCK-8 and oxygen-carrying phase-shift nanoparticles (PFP-O2-CCK8@lipid/TK-ICAM1 Ab nanoparticles, POC@L/TI NPs). These nanoparticles were designed for coronary artery endothelial cell targeting and responsiveness to dual stimuli. The results demonstrated that delayed myocardial contrast-enhanced echocardiography (DMCE) provided dynamic VR monitoring, with contrast intensity values showing a negative correlation with cardiac function parameter changes. POC@L/TI NPs significantly improved cardiac structural and functional parameters in rats with myocardial infarction and reperfusion and delayed the progression of heart failure by increasing tissue oxygenation, reducing the inflammatory response, inhibiting fibrotic scar formation and preventing myocardial cell apoptosis. This innovative approach combines supersaturated oxygen therapy with the multitarget therapeutic effect of CCK-8 and dynamic monitoring via DMCE to offer an integrated strategy for early detection and comprehensive VR treatment. Graphical abstract
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spelling doaj-art-077752a7eefb4a4f8f52bcb63b5960762025-08-20T02:48:22ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112310.1186/s12951-025-03183-7Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokininCan Wang0Hongfeng Cheng1Xiaoying Dong2Yue Zhan3Ying Liu4Nianhong Wu5Rui Tang6Hongye He7Yuting Cao8Liping Yang9Jianli Ren10Xingsheng Li11Pan Li12Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityFirst Department of Respiratory and Critical Care Medicine/Pneumoconiosis Department, The Second Hospital of Heilongjiang ProvinceDepartment of Geriatrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityDepartment of Geriatrics, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Ultrasound Molecular Imaging; State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical UniversityAbstract Early identification and treatment of ventricular remodeling (VR) are crucial for delaying the progression of heart failure after myocardial infarction. This study aims to develop a dual-responsive phase-shift molecular probe loaded with a cholecystokinin octapeptide (CCK-8) and oxygen, which will provide a new integrated scheme for the assessment and treatment of VR. Biocompatible phospholipid shells were utilized to encapsulate CCK-8 and perfluoropentane (PFP), an efficient oxygen carrier. Surface modification involves reactive oxygen species (ROS)-responsive thioketal (TK) bonds and anti-ICAM-1 antibodies to create CCK-8 and oxygen-carrying phase-shift nanoparticles (PFP-O2-CCK8@lipid/TK-ICAM1 Ab nanoparticles, POC@L/TI NPs). These nanoparticles were designed for coronary artery endothelial cell targeting and responsiveness to dual stimuli. The results demonstrated that delayed myocardial contrast-enhanced echocardiography (DMCE) provided dynamic VR monitoring, with contrast intensity values showing a negative correlation with cardiac function parameter changes. POC@L/TI NPs significantly improved cardiac structural and functional parameters in rats with myocardial infarction and reperfusion and delayed the progression of heart failure by increasing tissue oxygenation, reducing the inflammatory response, inhibiting fibrotic scar formation and preventing myocardial cell apoptosis. This innovative approach combines supersaturated oxygen therapy with the multitarget therapeutic effect of CCK-8 and dynamic monitoring via DMCE to offer an integrated strategy for early detection and comprehensive VR treatment. Graphical abstracthttps://doi.org/10.1186/s12951-025-03183-7Low-intensity focused ultrasoundVentricular remodelingMolecular imaging probeSupersaturated oxygen therapyCholecystokinin octapeptide
spellingShingle Can Wang
Hongfeng Cheng
Xiaoying Dong
Yue Zhan
Ying Liu
Nianhong Wu
Rui Tang
Hongye He
Yuting Cao
Liping Yang
Jianli Ren
Xingsheng Li
Pan Li
Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
Journal of Nanobiotechnology
Low-intensity focused ultrasound
Ventricular remodeling
Molecular imaging probe
Supersaturated oxygen therapy
Cholecystokinin octapeptide
title Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
title_full Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
title_fullStr Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
title_full_unstemmed Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
title_short Early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
title_sort early assessment and treatment of ventricular remodeling in vivo via a targeted ultrasonic molecular probe loaded with oxygen and cholecystokinin
topic Low-intensity focused ultrasound
Ventricular remodeling
Molecular imaging probe
Supersaturated oxygen therapy
Cholecystokinin octapeptide
url https://doi.org/10.1186/s12951-025-03183-7
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