Specific targeting of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells by polyethylene glycol-grafted polyethyleneimine modified with anti-HER2 single-domain antibody

Author:

Saqafi Batoul1,Rahbarizadeh Fatemeh1

Affiliation:

1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Polyethyleneimine is one of the most efficient non-viral gene delivery agents. However, some limitations such as non-specific cell binding, interactions with blood components, and relatively high cytotoxicity restrict its in vivo applications. In order to improve the properties of this molecule as a gene transfection vector, in this study, we developed a nano-carrier system based on polyethyleneimine derivatives synthesized by grafting bi-functional polyethylene glycol molecules (MAL-PEG3500-NHS) to 25 kDa branched polyethyleneimine polymer at three different molar ratios of 10, 20, and 30 (polyethylene glycol:polyethyleneimine). Variable domain of heavy-chain antibody against human epidermal growth factor receptor 2 as targeting agent was conjugated to polyethylene glycol–polyethyleneimine copolymer. In order to find the most effective resultant conjugate, the effect of these modifications on physicochemical properties, cytotoxicity, cellular uptake, and gene transfection efficiency of polyethyleneimine polymer was evaluated. According to the findings of this study and compared to unconjugated polyethyleneimine, PEGylated polyethyleneimine copolymers exhibit lower in vitro cytotoxicity. Polyethylene glycol–polyethyleneimine copolymer conjugated at a molar ratio of 10:1 (polyethylene glycol:polyethyleneimine) demonstrated a low cytotoxicity effect and desirable physicochemical properties. Anti-human epidermal growth factor receptor 2 variable domain of heavy-chain antibody conjugation further reduced the cytotoxicity of unmodified polyethyleneimine in all cell lines studied by 1.5- to 2-folds and also resulted in higher cellular uptake and transfection ability of this copolymer in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines versus normal breast cells or human epidermal growth factor receptor 2 negative cell lines. Altogether, our data suggested that variable domain of heavy-chain antibody–polyethylene glycol–polyethyleneimine copolymers might be an efficient nano-carrier system for specific targeting of human epidermal growth factor receptor 2 expressing tumors.

Publisher

SAGE Publications

Subject

Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3