文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

抗体功能化聚合物纳米颗粒用于将抗miR-21靶向递送至HER2阳性胃癌的增强抗增殖活性

Enhanced antiproliferative activity of antibody-functionalized polymeric nanoparticles for targeted delivery of anti-miR-21 to HER2 positive gastric cancer.

作者信息

Wu Feng-Lei, Zhang Jian, Li Wei, Bian Bao-Xiang, Hong Yi-Dong, Song Zi-Yan, Wang Hui-Yu, Cui Fang-Bo, Li Ru-Tian, Liu Qin, Jiang Xiao-Dong, Li Xiao-Min, Zheng Jun-Nian

机构信息

Department of Onology, Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu 222000, China.

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.

出版信息

Oncotarget. 2017 May 22;8(40):67189-67202. doi: 10.18632/oncotarget.18066. eCollection 2017 Sep 15.

DOI:10.18632/oncotarget.18066
PMID:28978026
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5620166/
Abstract

MiR-21 is an oncogenic miR frequently elevated in gastric cancer. Overexpression of miR-21 decreases the sensitivity of gastric cancer cells to trastuzumab, which is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2. However, optimization of miRNA or its anti-miRNA oligonucleotides (AMOs) for delivery is a challenge. Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including AMOs. This study is a continuation of our earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target gastric cancer cells with HER2 receptor over-expression using anti-miRNA-21 antisense oligonucleotides (AMO-21). The antibody conjugates (HER-PEG-PCL NPs) act against target cells via antibody-dependent mechanisms and also based on encapsutalated AMO-21. X-ray photoelectron spectroscopy validated the presence of trastuzumab on NP surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a stable antibody expression. The cell line specificity, cellular uptake, AMO-21 delivery, and cytotoxicity of the HER-PEG-PCL NPs were investigated. We found that the antibody conjugates significantly enhanced the cellular uptake of NPs. The HER-PEG-PCL NPs effectively suppressed the target miRNA expression in gastric cancer cells, which further up-regulated phosphatase and tensin homolog (PTEN). As a result, the sensitivity of HER2-expressing gastric cancer cells to trastuzumab was enhanced. The approach enhances the targeting by trastuzumab as well as antibody-dependent cellular cytotoxicity of immune effector cells. The antitumor effects of AMO-21-HER-PEG-PCL NPs were compared with trastuzumab in xenograft gastric cancer mice. The results provide insight into the biological and clinical potential of targeted AMO-21 delivery using modified trastuzumab for gastric cancer treatment.

摘要

微小RNA-21（miR-21）是一种在胃癌中经常上调的致癌性微小RNA。miR-21的过表达会降低胃癌细胞对曲妥珠单抗的敏感性，曲妥珠单抗是一种靶向人表皮生长因子受体2的人源化单克隆抗体。然而，优化用于递送的微小RNA或其抗微小RNA寡核苷酸（AMO）是一项挑战。受体介导的内吞作用在包括AMO在内的生物治疗药物的递送中起着关键作用。本研究是我们早期关于聚（ε-己内酯）（PCL）-聚（乙二醇）（PEG）纳米颗粒（PEG-PCL NPs）研究的延续，这些纳米颗粒用曲妥珠单抗包被，以使用抗微小RNA-21反义寡核苷酸（AMO-21）靶向过表达HER2受体的胃癌细胞。抗体偶联物（HER-PEG-PCL NPs）通过抗体依赖性机制以及基于包裹的AMO-21作用于靶细胞。X射线光电子能谱验证了曲妥珠单抗在纳米颗粒表面的存在。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）显示抗体表达稳定。研究了HER-PEG-PCL NPs的细胞系特异性、细胞摄取、AMO-21递送和细胞毒性。我们发现抗体偶联物显著增强了纳米颗粒的细胞摄取。HER-PEG-PCL NPs有效抑制了胃癌细胞中靶微小RNA的表达，进而上调了磷酸酶和张力蛋白同源物（PTEN）。结果，表达HER2的胃癌细胞对曲妥珠单抗的敏感性增强。该方法增强了曲妥珠单抗的靶向作用以及免疫效应细胞的抗体依赖性细胞毒性。在异种移植胃癌小鼠中比较了AMO-21-HER-PEG-PCL NPs与曲妥珠单抗的抗肿瘤作用。结果为使用修饰的曲妥珠单抗靶向递送AMO-21用于胃癌治疗的生物学和临床潜力提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/244854597730/oncotarget-08-67189-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/31461b05bd53/oncotarget-08-67189-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/a4c85d3e75ff/oncotarget-08-67189-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/e8db0b62a6ae/oncotarget-08-67189-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/fdf1ec1c4cd3/oncotarget-08-67189-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/c141be534a87/oncotarget-08-67189-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/f7a5d7749961/oncotarget-08-67189-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/244854597730/oncotarget-08-67189-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/31461b05bd53/oncotarget-08-67189-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/a4c85d3e75ff/oncotarget-08-67189-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/e8db0b62a6ae/oncotarget-08-67189-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/fdf1ec1c4cd3/oncotarget-08-67189-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/c141be534a87/oncotarget-08-67189-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/f7a5d7749961/oncotarget-08-67189-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83ee/5620166/244854597730/oncotarget-08-67189-g007.jpg

相似文献

[1]
Enhanced antiproliferative activity of antibody-functionalized polymeric nanoparticles for targeted delivery of anti-miR-21 to HER2 positive gastric cancer.

Oncotarget. 2017-5-22

[2]
Strengthening Gastric Cancer Therapy by Trastuzumab-Conjugated Nanoparticles with Simultaneous Encapsulation of Anti-MiR-21 and 5-Fluorouridine.

Cell Physiol Biochem. 2017

[3]
Multifunctional poly(D,L-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles decorated by Trastuzumab for targeted chemotherapy of breast cancer.

Biomaterials. 2008-2

[4]
Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab.

Int J Nanomedicine. 2015-3-18

[5]
Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models.

Clin Cancer Res. 2011-6-23

[6]
Engineering Chimeric Receptors To Investigate the Size- and Rigidity-Dependent Interaction of PEGylated Nanoparticles with Cells.

ACS Nano. 2016-1-13

[7]
Trastuzumab-functionalized nanoparticles of biodegradable copolymers for targeted delivery of docetaxel.

Nanomedicine (Lond). 2009-6

[8]
Formulation of Anti-miR-21 and 4-Hydroxytamoxifen Co-loaded Biodegradable Polymer Nanoparticles and Their Antiproliferative Effect on Breast Cancer Cells.

Mol Pharm. 2015-6-1

[9]
The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab.

Ann Surg Oncol. 2014-1

[10]
Targeted delivery of antisense inhibitor of miRNA for antiangiogenesis therapy using cRGD-functionalized nanoparticles.

Mol Pharm. 2010-12-21

引用本文的文献

[1]
Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Adv Ther (Weinh). 2023-3

[2]
Nanoparticle-Delivered Transforming Growth Factor-β1 siRNA Induces PD-1 against Gastric Cancer by Transforming the Phenotype of the Tumor Immune Microenvironment.

Pharmaceuticals (Basel). 2022-11-29

[3]
Polymeric Carriers for Delivery of RNA Cancer Therapeutics.

Noncoding RNA. 2022-8-2

[4]
Application of Dendrimers in Anticancer Diagnostics and Therapy.

Molecules. 2022-5-18

[5]
Notch Intracellular Domain Plasmid Delivery via Poly(Lactic-Co-Glycolic Acid) Nanoparticles to Upregulate Notch Pathway Molecules.

Front Cardiovasc Med. 2021-9-28

[6]
Research Progress in microRNA-Based Therapy for Gastric Cancer.

Onco Targets Ther. 2019-12-24

[7]
RNA Micelles for the Systemic Delivery of Anti-miRNA for Cancer Targeting and Inhibition without Ligand.

ACS Nano. 2018-12-19

[8]
Non-viral based miR delivery and recent developments.

Eur J Pharm Biopharm. 2018-4-19

[9]
Targeted Delivery of Doxorubicin via CD147-Mediated ROS/pH Dual-Sensitive Nanomicelles for the Efficient Therapy of Hepatocellular Carcinoma.

AAPS J. 2018-2-23

[10]
Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.

Int J Nanomedicine. 2017-11-28

本文引用的文献

[1]
Cancer statistics in China, 2015.

CA Cancer J Clin. 2016-1-25

[2]
Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

J Clin Oncol. 2015-11-20

[3]
Trastuzumab Inhibits Growth of HER2-Negative Gastric Cancer Cells Through Gastrin-Initialized CCKBR Signaling.

Dig Dis Sci. 2015-12

[4]
Therapeutic targeting of microRNAs: current status and future challenges.

Nat Rev Drug Discov. 2014-7-11

[5]
Functional genetic approach identifies MET, HER3, IGF1R, INSR pathways as determinants of lapatinib unresponsiveness in HER2-positive gastric cancer.

Clin Cancer Res. 2014-6-27

[6]
The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice.

J Control Release. 2014-1-10

[7]
PEG-PCL-DEX polymersome-protamine vector as an efficient gene delivery system via PEG-guided self-assembly.

Nanomedicine (Lond). 2013-12-3

[8]
The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab.

Ann Surg Oncol. 2014-1

[9]
Improved Performance of Anti-miRNA Oligonucleotides Using a Novel Non-Nucleotide Modifier.

Mol Ther Nucleic Acids. 2013-8-27

[10]
MiR-215 modulates gastric cancer cell proliferation by targeting RB1.

Cancer Lett. 2013-8-24

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索