Nano Self-Assemblies of Caffeic Acid-Fibronectin Mimic a Peptide Conjugate for the Treatment of Corneal Epithelial Injury

被引：6

作者：

Wu, Yiping ^{[1
]}

Du, Lulu ^{[1
]}

Xu, Xiaoning ^{[1
]}

Hu, Yuhan ^{[1
]}

Liu, Jia ^{[1
]}

Zhang, Jingwei ^{[1
]}

Lei, Lei ^{[1
]}

He, Wenfang ^{[1
]}

Sheng, Zihao ^{[1
]}

Ni, Yuanao ^{[1
]}

Qu, Jia ^{[1
]}

Li, Xingyi ^{[1
]}

Jiang, Jun ^{[1
]}

机构：

[1] Wenzhou Med Univ, Eye Hosp, Natl Engn Res Ctr Ophthalmol & Optometry, Wenzhou 325027, Peoples R China

来源：

MOLECULAR PHARMACEUTICS | 2023年 / 20卷 / 11期

基金：

中国国家自然科学基金;

关键词：

antioxidant; anti-inflammatory; corneal epithelialinjury; self-assembly; nanoparticle; CELL-BINDING SITE; GROWTH-FACTORS; PHENETHYL ESTER; INTEGRINS; MATRIX; ANTIOXIDANT; INHIBITION; MODULATION; MIGRATION; TISSUE;

D O I：

10.1021/acs.molpharmaceut.3c00861

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Rapid corneal re-epithelialization is important for corneal wound healing. Corneal epithelial cell motility and oxidative stress are important targets for therapeutic intervention. In this study, we covalently conjugated the antioxidant caffeic acid (CA) with a bioactive peptide sequence (PHSRN) to generate a CA-PHSRN amphiphile, which was formulated into nanoparticular eye drops with an average size of 43.21 +/- 16 nm. CA-PHSRN caused minimal cytotoxicity against human corneal epithelial cells (HCECs) and RAW264.7 cells, exhibited an excellent free radical scavenging ability, and remarkably attenuated reactive oxygen species (ROS) levels in H2O2-stimulated HCECs. The antioxidant and anti-inflammatory activities of CA-PHSRN were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results show that CA-PHSRN treatment effectively prevented LPS-induced DNA damage and significantly reduced the levels of LPS-induced pro-inflammatory cytochemokines (i.e., iNOS, NO, TNF-alpha, IL-6, and COX-2) in a dose-dependent manner. Moreover, using a rabbit corneal epithelial ex vivo migration assay, we demonstrated that the proposed CA-PHSRN accelerated corneal epithelial cell migration and exhibited high ocular tolerance and ocular bioavailability after topical instillation. Taken together, the proposed CA-PHSRN nanoparticular eye drops are a promising therapeutic formulation for the treatment of corneal epithelial injury.

引用

页码：5937 / 5946

页数：10

共 56 条

[1] Caffeic Acid Phenethyl Ester: Its Protective Role Against Certain Major Eye Diseases [J].

Akyol, Sumeyya ;

Ugurcu, Veli ;

Balci, Mehmet ;

Gurel, Ayse ;

Erden, Gonul ;

Cakmak, Ozlem ;

Akyol, Omer .

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 2014, 30 (09) :700-708

[2] Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-β C-terminal peptides [J].

Arai, Takuya ;

Ohno, Akiko ;

Mori, Kazunori ;

Kuwata, Hiroshi ;

Mizuno, Mirei ;

Imai, Kohei ;

Hara, Shuntaro ;

Shibanuma, Motoko ;

Kurihara, Masaaki ;

Miyata, Naoki ;

Nakagawa, Hidehiko ;

Fukuhara, Kiyoshi .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (22) :5468-5471

[3] The role of integrins in corneal wound healing [J].

Carter, Renee T. .

VETERINARY OPHTHALMOLOGY, 2009, 12 :2-9

[4] Anatomy and physiology of the cornea [J].

DelMonte, Derek W. ;

Kim, Terry .

JOURNAL OF CATARACT AND REFRACTIVE SURGERY, 2011, 37 (03) :588-598

[5] Multifunctional Supramolecular Filament Hydrogel Boosts Anti-Inflammatory Efficacy In Vitro and In Vivo [J].

Deng, Jie ;

Lin, Deqing ;

Ding, Xiangyu ;

Wang, Yuan ;

Hu, YuHan ;

Shi, Hui ;

Chen, Lin ;

Chu, Bingyang ;

Lei, Lei ;

Wen, Chunmei ;

Wang, Jiaqing ;

Qian, Zhiyong ;

Li, Xingyi .

ADVANCED FUNCTIONAL MATERIALS, 2022, 32 (16)

[6] Inhibition of inflammatory cytokine production in human corneal cells by dexamethasone, but not cyclosporin [J].

Djalilian, Ali R. ;

Nagineni, Chandrasekharam N. ;

Mahesh, Sankanaranayana P. ;

Smith, Janine A. ;

Nussenblatt, Robert B. ;

Hooks, John J. .

CORNEA, 2006, 25 (06) :709-714

[7] CORNEAL EPITHELIAL WOUND-HEALING [J].

DUA, HS ;

GOMES, JAP ;

SINGH, A .

BRITISH JOURNAL OF OPHTHALMOLOGY, 1994, 78 (05) :401-408

[8] Overview of the Cornea: Structure, Function, and Development [J].

Eghrari, Allen O. ;

Riazuddin, S. Amer ;

Gottsch, John D. .

MOLECULAR BIOLOGY OF EYE DISEASE, 2015, 134 :7-23

[9] Effects of transforming growth factor-beta 2, interleukin 6 and fibronectin on corneal epithelial wound healing [J].

Er, H ;

Uzmez, E .

EUROPEAN JOURNAL OF OPHTHALMOLOGY, 1998, 8 (04) :224-229

[10] Boundary crossing in epithelial wound healing [J].

Fong, Eileen ;

Tzlil, Shelly ;

Tirrell, David A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (45) :19302-19307

← 1 2 3 4 5 6 →