Augmented liver targeting of exosomes by surface modification with cationized pullulan

普鲁兰 去唾液酸糖蛋白受体 微泡 外体 表面改性 细胞生物学 化学 肝细胞 体外 生物物理学 生物化学 生物 多糖 小RNA 基因 物理化学
作者
Ryo Tamura,Shinji Üemoto,Yasuhiko Tabata
出处
期刊:Acta Biomaterialia [Elsevier BV]
卷期号:57: 274-284 被引量:164
标识
DOI:10.1016/j.actbio.2017.05.013
摘要

Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes. Surface modification can be achieved by a simple mixing of original exosomes and cationized pullulan and through an electrostatic interaction of both substances. The exosomes modified with cationized pullulan were internalized into HepG2 cells in vitro to a significantly greater extent than unmodified ones and this internalization was induced through the asialoglycoprotein receptor that was specifically expressed on HepG2 cells and hepatocytes. When injected intravenously into mice with concanavalin A-induced liver injury, the modified exosomes accumulated in the liver tissue, resulting in an enhanced anti-inflammatory effect in vivo. It is concluded that the surface modification with cationized pullulan promoted accumulation of the exosomes in the liver and the subsequent biological function, resulting in a greater therapeutic effect on liver injury. Exosomes have shown potentials as therapeutics for various inflammatory disease models. This study is the first to show the specific accumulation of exosomes in the liver and enhanced anti-inflammatory effect via the surface modification of exosomes using pullulan, which is specifically recognized by the asialoglycoprotein receptor (AGPR) on HepG2 cells and hepatocytes. The pullulan was expressed on the surface of PKH-labeled exosomes, and it led increased accumulation of PKH into HepG2 cells, whereas the accumulation was canceled by AGPR inhibitor. In the mouse liver injury model, the modification of PKH-labeled exosomes with pullulan enabled increased accumulation of PKH specifically in the injured liver. Furthermore the greater therapeutic effects against the liver injury compared with unmodified original exosomes was observed.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
似水流年完成签到 ,获得积分10
刚刚
sysi完成签到 ,获得积分10
15秒前
绿波电龙完成签到,获得积分10
16秒前
19秒前
ZZzz完成签到 ,获得积分10
20秒前
wujiwuhui发布了新的文献求助10
24秒前
26秒前
梦梦的小可爱完成签到 ,获得积分10
26秒前
xinjie发布了新的文献求助10
29秒前
31秒前
蛋花肉圆汤完成签到,获得积分10
31秒前
羞涩的文轩完成签到 ,获得积分10
32秒前
37秒前
38秒前
北城完成签到 ,获得积分10
40秒前
量子星尘发布了新的文献求助10
40秒前
43秒前
爱听歌电灯胆完成签到 ,获得积分10
43秒前
不爱吃西葫芦完成签到 ,获得积分10
44秒前
申燕婷完成签到 ,获得积分10
45秒前
橙子完成签到 ,获得积分10
47秒前
ruochenzu发布了新的文献求助10
47秒前
fusheng完成签到 ,获得积分10
56秒前
浮生完成签到 ,获得积分10
1分钟前
xinjie完成签到,获得积分10
1分钟前
Will完成签到,获得积分10
1分钟前
cuddly完成签到 ,获得积分10
1分钟前
掉头发的小白完成签到,获得积分10
1分钟前
不想看文献完成签到 ,获得积分10
1分钟前
1分钟前
当女遇到乔完成签到 ,获得积分10
1分钟前
独行者完成签到,获得积分10
1分钟前
眼睛大的电脑完成签到,获得积分10
1分钟前
1分钟前
敏敏发布了新的文献求助10
1分钟前
木木完成签到 ,获得积分10
1分钟前
量子星尘发布了新的文献求助10
1分钟前
JamesPei应助科研通管家采纳,获得10
1分钟前
彭于晏应助科研通管家采纳,获得10
1分钟前
如意2023完成签到 ,获得积分10
1分钟前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038066
求助须知:如何正确求助?哪些是违规求助? 3575779
关于积分的说明 11373801
捐赠科研通 3305584
什么是DOI,文献DOI怎么找? 1819239
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022