已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Collagenase Type I and Probucol-Loaded Nanoparticles Penetrate the Extracellular Matrix to Target Hepatic Stellate Cells for Hepatic Fibrosis Therapy

肝星状细胞 细胞外基质 肝纤维化 纤维化 癌症研究 CD44细胞 细胞生物学 肝硬化 内化 化学 材料科学 医学 病理 生物 受体 内科学 生物化学 细胞
作者
Xiaowei Wang,Wenjun Zhang,Sheng Zeng,Liudi Wang,Bin Wang
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:175: 262-278 被引量:4
标识
DOI:10.1016/j.actbio.2023.12.027
摘要

Hepatic fibrosis is a common pathological process in chronic liver diseases, characterized by excessive reactive oxygen species (ROS), activated hepatic stellate cells (HSCs), and massive synthesis of extracellular matrix (ECM), which are important factors in the development of liver cirrhosis, liver failure, and liver cancer. During the development of hepatic fibrosis, ECM collagen produced by activated HSCs significantly hinders medication delivery to targeted cells and reduces the efficiency of pharmacological therapy. In this study, we designed a multifunctional hyaluronic acid polymeric nanoparticle (HA@PRB/COL NPs) based on autophagy inhibitor probucol (PRB) and collagenase type I (COL) modification, which could enhance ECM degradation and accurately target HSCs through specificity binding CD44 receptor in hepatic fibrosis therapy. Upon encountering excessive collagen I-deposition formed barrier, HA@PRB/COL NPs performed the nanodrill-like function to effectively degrade pericellular collagen I, leading to greater ECM penetration and prominent HSCs internalization capacity of delivered PRB. In mouse hepatic fibrosis model, HA@PRB/COL NPs were efficiently delivered to HSCs through binding CD44 receptor to achieve efficient accumulation in fibrotic liver. Further, we showed that HA@PRB/COL NPs executed the optimal anti-fibrotic activity by inhibiting autophagy and activation of HSCs. In conclusion, our novel dual-functional co-delivery system with degrading fibrotic ECM collagen and targeting activated HSCs exhibits great potentials in the treatment of hepatic fibrosis in clinic. The excess release of extracellular matrix (ECM) such as collagen in hepatic fibrosis hinders medication delivery and decreases the efficiency of pharmacological drugs. We aimed to develop a nano-delivery carrier system with protein hydrolyzed surfaces and further encapsulated an autophagy inhibitor (PRB) to enhance fibrosis-related ECM degradation-penetration and hepatic stellate cells (HSCs) targeting in hepatic fibrosis niche (HA@PRB/COL NPs). The COL of HA@PRB/COL NPs successfully worked as a scavenger to promote the digestion of the ECM collagen I barrier for deeper penetration into fibroid liver tissue. It also accurately targeted HSCs through specifically binding to the CD44 receptor and subsequently released PRB to inhibit autolysosome and ROS generation, thus preventing HSCs activation. Our HA@PRB/COL NPs system provided a promising therapeutic strategy for hepatic fibrosis in a clinic setting.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
水野发布了新的文献求助10
刚刚
麻瓜发布了新的文献求助10
1秒前
虚心完成签到 ,获得积分10
2秒前
2秒前
追寻的问玉完成签到 ,获得积分10
2秒前
lzzao发布了新的文献求助10
3秒前
南风知意发布了新的文献求助10
3秒前
3秒前
陈星锦发布了新的文献求助10
4秒前
lanshuitai发布了新的文献求助10
6秒前
摇摇奶昔完成签到,获得积分20
7秒前
7秒前
10秒前
高高完成签到,获得积分20
10秒前
10秒前
TAKI发布了新的文献求助10
11秒前
孤独的乾发布了新的文献求助10
13秒前
高高发布了新的文献求助10
15秒前
可爱的柜子应助陈星锦采纳,获得10
16秒前
依依完成签到 ,获得积分10
16秒前
Orange应助gery采纳,获得10
17秒前
18秒前
田様应助加油采纳,获得10
18秒前
麻瓜发布了新的文献求助10
21秒前
迷路的曼梅完成签到,获得积分10
22秒前
锂炸发布了新的文献求助10
23秒前
Lucas应助温良恭俭让采纳,获得10
24秒前
CodeCraft应助TAKI采纳,获得10
24秒前
midoli完成签到,获得积分10
25秒前
26秒前
28秒前
temaxs完成签到 ,获得积分10
30秒前
Orange应助锂炸采纳,获得10
31秒前
加油发布了新的文献求助10
31秒前
辛勤的雨安完成签到,获得积分20
31秒前
盐湖所王裕民完成签到,获得积分20
34秒前
Bowman完成签到,获得积分10
35秒前
35秒前
38秒前
38秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Very-high-order BVD Schemes Using β-variable THINC Method 830
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3248577
求助须知:如何正确求助?哪些是违规求助? 2892029
关于积分的说明 8269412
捐赠科研通 2560089
什么是DOI,文献DOI怎么找? 1388851
科研通“疑难数据库(出版商)”最低求助积分说明 650913
邀请新用户注册赠送积分活动 627798