Enhanced Liposomal Drug Delivery Via Membrane Fusion Triggered by Dimeric Coiled‐Coil Peptides

Author:

Zeng Ye1,Shen Mengjie1,Singhal Ankush1,Sevink Geert Jan Agur1,Crone Niek1,Boyle Aimee L.1,Kros Alexander1ORCID

Affiliation:

1. Dept. Supramolecular & Biomaterials Chemistry Leiden Institute of Chemistry Leiden University Einsteinweg 55 Leiden 2333 CC The Netherlands

Abstract

AbstractAn ideal nanomedicine system improves the therapeutic efficacy of drugs. However, most nanomedicines enter cells via endosomal/lysosomal pathways and only a small fraction of the cargo enters the cytosol inducing therapeutic effects. To circumvent this inefficiency, alternative approaches are desired. Inspired by fusion machinery found in nature, synthetic lipidated peptide pair E4/K4 is used to induce membrane fusion previously. Peptide K4 interacts specifically with E4, and it has a lipid membrane affinity and resulting in membrane remodeling. To design efficient fusogens with multiple interactions, dimeric K4 variants are synthesized to improve fusion with E4‐modified liposomes and cells. The secondary structure and self‐assembly of dimers are studied; the parallel PK4 dimer forms temperature‐dependent higher‐order assemblies, while linear K4 dimers form tetramer‐like homodimers. The structures and membrane interactions of PK4 are supported by molecular dynamics simulations. Upon addition of E4, PK4 induced the strongest coiled‐coil interaction resulting in a higher liposomal delivery compared to linear dimers and monomer. Using a wide spectrum of endocytosis inhibitors, membrane fusion is found to be the main cellular uptake pathway. Doxorubicin delivery results in efficient cellular uptake and concomitant antitumor efficacy. These findings aid the development of efficient delivery systems of drugs into cells using liposome‐cell fusion strategies.

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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