Bioengineered Human Serum Albumin Fusion Protein as Target/Enzyme/pH Three-Stage Propulsive Drug Vehicle for Tumor Therapy

白蛋白 药品 血清白蛋白 人白蛋白 牛血清白蛋白 阿霉素 材料科学 靶向给药 体外 生物化学
作者
Mingyu Wang,Li Zhang,Yanfei Cai,Yang Yang,Lipeng Qiu,Yiting Shen,Jian Jin,Juan Zhou,Jinghua Chen
出处
期刊:ACS Nano [American Chemical Society]
卷期号:14 (12): 17405-17418 被引量:8
标识
DOI:10.1021/acsnano.0c07610
摘要

Human serum albumin (HSA) has the characteristics of biocompatibility and long circulation, which is widely used as the carrier of insoluble anticancer drugs, but it also has some disadvantages such as weak tumor targeting and uncontrollable drug release. Herein, HSA was modified to improve its biological performance by introducing polyhistidine (pHis), matrix metalloproteinase-2 (MMP-2) digestion, and Arg-Gly-Asp (RGD) peptide at the separated end of HSA through gene fusion technology. The resulting protein expressed by Pichia pastoris could self-assemble into 3RGD-HSA-MMP-18His nanoparticles (RHMH18 NPs) accompanied by loading hydrophobic drug paclitaxel (PTX) into the polyhistidine micelle core. RHMH18 NPs exhibited active tumor targeting in high efficiency owing to the RGD-mediated specific binding toward ανβ3-integrin upregulated on tumor vasculature endothelium, resulting in the enrichment of therapeutic substances in tumor sites. Once reaching the tumor microenvironment, RHMH18 NPs was cut off by MMP-2 to remove the HSA-3RGD moiety, leaving the small and positively charged histidine micelle, which could penetrate the deep part of tumor tissue more effectively. Finally, the histidine micelle escaped from lysosome successfully and released drug in response to pH. The in vivo experiments' results demonstrated that the three-stage propulsion RHMH18 NPs presented superior tumor inhibition activity with minimal side effects, providing potential strategies of protein based drug delivery systems for tumor therapy.
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
氘代乙腈是不贵的呀完成签到,获得积分10
1秒前
1秒前
默默的大白完成签到,获得积分10
1秒前
2秒前
Jasper应助eyu采纳,获得20
2秒前
小小发布了新的文献求助10
2秒前
4秒前
大模型应助大厨懒洋洋采纳,获得10
4秒前
asd发布了新的文献求助10
4秒前
dby发布了新的文献求助10
5秒前
大帅哥发布了新的文献求助10
5秒前
iNk应助半芹采纳,获得20
6秒前
6秒前
7秒前
斯文败类应助Du采纳,获得30
8秒前
冷酷云朵完成签到,获得积分10
9秒前
小c完成签到 ,获得积分10
9秒前
bxb发布了新的文献求助10
10秒前
10秒前
韵寒完成签到 ,获得积分10
11秒前
kakka关注了科研通微信公众号
13秒前
14秒前
寻道图强应助xiaosu采纳,获得30
14秒前
幸福胡萝卜完成签到,获得积分10
15秒前
16秒前
16秒前
17秒前
科目三应助chenxin7271采纳,获得10
17秒前
小白发布了新的文献求助10
18秒前
光伏吴彦祖完成签到,获得积分10
18秒前
19秒前
大力南风完成签到,获得积分10
19秒前
小白菜发布了新的文献求助10
19秒前
20秒前
张小星发布了新的文献求助10
21秒前
777777完成签到,获得积分10
21秒前
Jamer发布了新的文献求助10
22秒前
Greetdawn发布了新的文献求助10
22秒前
22秒前
23秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
An Introduction to Geographical and Urban Economics: A Spiky World Book by Charles van Marrewijk, Harry Garretsen, and Steven Brakman 600
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 400
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 3153624
求助须知:如何正确求助?哪些是违规求助? 2804799
关于积分的说明 7861757
捐赠科研通 2462835
什么是DOI,文献DOI怎么找? 1311002
科研通“疑难数据库(出版商)”最低求助积分说明 629428
版权声明 601821