Synthesis and characterization of Gd-DTPA/fucoidan/peptide complex nanoparticle and in vitro magnetic resonance imaging of inflamed endothelial cells

Tsai-Mu Cheng; Rou Li; Yu-Chieh Jill Kao; Chun-Hua Hsu; Hsueh-Liang Chu; Kun-Ying Lu; Chun A Changou; Che-Chang Chang; Lee-Hsin Chang; Min-Lang Tsai; Fwu-Long Mi

doi:10.1016/j.msec.2020.111064

Synthesis and characterization of Gd-DTPA/fucoidan/peptide complex nanoparticle and in vitro magnetic resonance imaging of inflamed endothelial cells

Mater Sci Eng C Mater Biol Appl. 2020 Sep:114:111064. doi: 10.1016/j.msec.2020.111064. Epub 2020 May 11.

Authors

Affiliations

¹ Graduate Institute of Translational Medicine, College of Medicine and Technology, Taipei Medical University, Taipei 11031, Taiwan.
² Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan.
³ Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁴ Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan.
⁵ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁶ Graduate Institute of Translational Medicine, College of Medicine and Technology, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Sciences and Technology, Taipei Medical University, Taipei, Taiwan.
⁷ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁸ Department of Food Science, College of Life Sciences, National Taiwan Ocean University, Keelung 20224, Taiwan. Electronic address: tsai5122@gmail.com.
⁹ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Department of Biochemistry and Molecular Cell Biology, School of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: flmi530326@tmu.edu.tw.

PMID: 32994013
DOI: 10.1016/j.msec.2020.111064

Abstract

P-selectin overexpressed on activated endothelial cells and platelets is a new target for treatment of cancers and cardiovascular diseases such as atherosclerosis and thrombosis. In this study, depolymerized low molecular weight fucoidan (LMWF₈₇₇₅) and a thermolysin-hydrolyzed protamine peptide (TPP₁₈₈₀) were prepared. TPP₁₈₈₀ and LMWF₈₇₇₅ were able to form self-assembled complex nanoparticles (CNPs). The formation of TPP₁₈₈₀/LMWF₈₇₇₅ CNPs was characterized by Fourier-transform infrared spectra, circular dichroism spectra and isothermal titration calorimetry. The CNPs selectively targeted PMA-stimulated, inflamed endothelial cells (HUVECs) with high expression of P-selectin. Gd-DTPA MRI contrast agent was successfully loaded in the CNPs with better T₁ relaxivity and selectively accumulated in the activated HUVECs with increased MRI intensity and reduced cytotoxicity as compared to free Gd-DTPA. Our results suggest that the TPP₁₈₈₀/LMWF₈₇₇₅ CNPs may have potential in future for early diagnosis of cardiovascular diseases and cancers in which the endothelium is inflamed or activated.

Keywords: Cell penetrating peptide; Drug delivery; Fucoidan; Imaging; Nanoparticles; Targeting.

MeSH terms

Contrast Media
Endothelial Cells
Endothelium
Gadolinium DTPA*
Magnetic Resonance Imaging
Nanoparticles*
Peptides
Polysaccharides

Substances

Contrast Media
Peptides
Polysaccharides
fucoidan
Gadolinium DTPA