Size-dependent interactions between calciprotein particles and vascular endothelium

The underlying mechanisms governing the interactions between nanoparticles and vascular endothelial barrier remain largely unexplored, which is crucial for the optimal design of nanoparticles for clinical applications. In this study, the size-dependent interactions between calciprotein particles (CP...

Full description

Saved in:
Bibliographic Details
Main Authors: Zeping Zhang, Xinyue Wang, Caihao Huang, Meixia Wang, Wei Cui, Liang Hao, Rui Yang, Hong-hui Wang, Xing Zhang
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425001577
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849715605382365184
author Zeping Zhang
Xinyue Wang
Caihao Huang
Meixia Wang
Wei Cui
Liang Hao
Rui Yang
Hong-hui Wang
Xing Zhang
author_facet Zeping Zhang
Xinyue Wang
Caihao Huang
Meixia Wang
Wei Cui
Liang Hao
Rui Yang
Hong-hui Wang
Xing Zhang
author_sort Zeping Zhang
collection DOAJ
description The underlying mechanisms governing the interactions between nanoparticles and vascular endothelial barrier remain largely unexplored, which is crucial for the optimal design of nanoparticles for clinical applications. In this study, the size-dependent interactions between calciprotein particles (CPPs) and endothelial cells (ECs) were investigated using a rat model of chronic kidney disease (CKD) induced by 5/6 nephrectomy. Two primary types of CPP1 were studied: small-sized CPP1 (S-CPP1, <50 nm) and larger CPP1 (L-CPP1, <100 nm), detected three and five weeks post-surgery, respectively. By adjusting the amounts of Ca2+, HPO42− and H2PO4− ions in Dulbecco's Modified Eagle Medium supplemented with 10 % (V/V) fetal bovine serum and 1 % (V/V) Pen-Strep solution, S-CPP1 (<50 nm) with an elliptical shape, L-CPP1 (50–100 nm), and secondary CPPs (CPP2, >100 nm) with a needle-like crystalline structure, resembling endogenous CPPs, were synthesized. The results showed that S-CPP1 significantly increased endothelial permeability at concentrations of 445 μg/mL and 890 μg/mL, thereby disrupting the integrity of the endothelial barrier formed by a confluent monolayer of ECs. Immunofluorescence analysis revealed that L-CPP1 was internalized by ECs via endocytosis, while S-CPP1 disrupted VE-cadherin junctions, leading to irregular cell morphology and widened intercellular gaps. These structural changes likely contribute to medial calcification as CPPs accumulate within the circulatory system. In conclusion, the findings underscore that the interaction between CPPs and the vascular endothelium is strongly size-dependent, with significant implications for vascular system health and the design of nanoparticle-based therapies.
format Article
id doaj-art-bdd8e1027507456699b2aefd3b804c6b
institution DOAJ
issn 2590-0064
language English
publishDate 2025-04-01
publisher Elsevier
record_format Article
series Materials Today Bio
spelling doaj-art-bdd8e1027507456699b2aefd3b804c6b2025-08-20T03:13:18ZengElsevierMaterials Today Bio2590-00642025-04-013110159910.1016/j.mtbio.2025.101599Size-dependent interactions between calciprotein particles and vascular endotheliumZeping Zhang0Xinyue Wang1Caihao Huang2Meixia Wang3Wei Cui4Liang Hao5Rui Yang6Hong-hui Wang7Xing Zhang8Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, Dalian University of Technology, Dalian, Liaoning 116024, ChinaState Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Biology, Hunan University, Changsha, Hunan 410082, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, ChinaSchool of Forensic Medicine, China Medical University, Shenyang, Liaoning 110026, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, ChinaState Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Biology, Hunan University, Changsha, Hunan 410082, China; Corresponding author.Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China; Corresponding author. Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China.The underlying mechanisms governing the interactions between nanoparticles and vascular endothelial barrier remain largely unexplored, which is crucial for the optimal design of nanoparticles for clinical applications. In this study, the size-dependent interactions between calciprotein particles (CPPs) and endothelial cells (ECs) were investigated using a rat model of chronic kidney disease (CKD) induced by 5/6 nephrectomy. Two primary types of CPP1 were studied: small-sized CPP1 (S-CPP1, <50 nm) and larger CPP1 (L-CPP1, <100 nm), detected three and five weeks post-surgery, respectively. By adjusting the amounts of Ca2+, HPO42− and H2PO4− ions in Dulbecco's Modified Eagle Medium supplemented with 10 % (V/V) fetal bovine serum and 1 % (V/V) Pen-Strep solution, S-CPP1 (<50 nm) with an elliptical shape, L-CPP1 (50–100 nm), and secondary CPPs (CPP2, >100 nm) with a needle-like crystalline structure, resembling endogenous CPPs, were synthesized. The results showed that S-CPP1 significantly increased endothelial permeability at concentrations of 445 μg/mL and 890 μg/mL, thereby disrupting the integrity of the endothelial barrier formed by a confluent monolayer of ECs. Immunofluorescence analysis revealed that L-CPP1 was internalized by ECs via endocytosis, while S-CPP1 disrupted VE-cadherin junctions, leading to irregular cell morphology and widened intercellular gaps. These structural changes likely contribute to medial calcification as CPPs accumulate within the circulatory system. In conclusion, the findings underscore that the interaction between CPPs and the vascular endothelium is strongly size-dependent, with significant implications for vascular system health and the design of nanoparticle-based therapies.http://www.sciencedirect.com/science/article/pii/S2590006425001577EndotheliumCalciprotein nanoparticlesChronic kidney diseaseBiomimetic synthesis
spellingShingle Zeping Zhang
Xinyue Wang
Caihao Huang
Meixia Wang
Wei Cui
Liang Hao
Rui Yang
Hong-hui Wang
Xing Zhang
Size-dependent interactions between calciprotein particles and vascular endothelium
Materials Today Bio
Endothelium
Calciprotein nanoparticles
Chronic kidney disease
Biomimetic synthesis
title Size-dependent interactions between calciprotein particles and vascular endothelium
title_full Size-dependent interactions between calciprotein particles and vascular endothelium
title_fullStr Size-dependent interactions between calciprotein particles and vascular endothelium
title_full_unstemmed Size-dependent interactions between calciprotein particles and vascular endothelium
title_short Size-dependent interactions between calciprotein particles and vascular endothelium
title_sort size dependent interactions between calciprotein particles and vascular endothelium
topic Endothelium
Calciprotein nanoparticles
Chronic kidney disease
Biomimetic synthesis
url http://www.sciencedirect.com/science/article/pii/S2590006425001577
work_keys_str_mv AT zepingzhang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT xinyuewang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT caihaohuang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT meixiawang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT weicui sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT lianghao sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT ruiyang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT honghuiwang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium
AT xingzhang sizedependentinteractionsbetweencalciproteinparticlesandvascularendothelium