ICCAS OpenIR  > 分子纳米结构与纳米技术实验室
Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment
Zhao, Xiao1,2,3; Wang, Xiuchao3; Sun, Wei3,7,8; Cheng, Keman1,2; Qin, Hao1,2; Han, Xuexiang1,2; Lin, Yu6; Wang, Yongwei1,2; Lang, Jiayan1,2; Zhao, Ruifang1,2; Zheng, Xiaowei3; Zhao, Ying1,2; Shi, Jian1,2; Hao, Jihui3; Miao, Qing Robert1,2,4,5; Nie, Guangjun1,2; Ren, He3
2018-03-01
Source PublicationBIOMATERIALS
Volume158Pages:44-55
AbstractLow chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Using immunohistochemical evaluation, we investigated that decreased expression of human equilibrative nucleoside transporter-1 (hENT1, which is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity. To solve these problems, we employed a nanomedicine-based formulation of cationic liposomes for co-delivery of GEM along with siRNA targeting RRM2. Due to the specific endocytic uptake mechanism of nanocarriers and gene silencing effect of RRM2 siRNA, this nanomedicine formulation significantly increased GEM chemosensitivity in tumor models of genetically engineered Panc1 cells with low hENT1 or high RRM2 expression. Moreover, in a series of patient-derived cancer cells, we demonstrated that the therapeutic benefits of the nanomedicine formulations were associated with the expression levels of hENT1 and RRM2. In summary, we found that the essential factors of GEM chemosensitivity were the expression levels of hENT1 and RRM2, and synthesized nanoformulations can overcome these problems. This unique design of nanomedicine not only provides a universal platform to enhance chemosensitivity but also contributes to the precision design and personalized treatment in nanomedicine. (C) 2017 Elsevier Ltd. All rights reserved.
KeywordNanocarriers Gemcitabine Pancreatic Ductal Adenocarcinoma Hent1 Rrm2
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/38476
Collection分子纳米结构与纳米技术实验室
Affiliation1.Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China
2.Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, 11 Beiyitiao, Beijing 100190, Peoples R China
3.Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Dept Pancreat Carcinoma, Tianjin 300060, Peoples R China
4.Med Coll Wisconsin, Dept Pathol, Childrens Res Inst, Div Pediat Surg,Dept Surg, Milwaukee, WI 53226 USA
5.Med Coll Wisconsin, Childrens Res Inst, Dept Pathol, Div Pediat Pathol, Milwaukee, WI 53226 USA
6.CAS Key Lab Analyt Chem Living Biosyst, Zhongguancun North First St 2, Beijing 100190, Peoples R China
7.Fudan Univ, Shanghai Canc Ctr, Inst Canc, Dept Breast Surg, Shanghai, Peoples R China
8.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China
Recommended Citation
GB/T 7714
Zhao, Xiao,Wang, Xiuchao,Sun, Wei,et al. Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment[J]. BIOMATERIALS,2018,158:44-55.
APA Zhao, Xiao.,Wang, Xiuchao.,Sun, Wei.,Cheng, Keman.,Qin, Hao.,...&Ren, He.(2018).Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment.BIOMATERIALS,158,44-55.
MLA Zhao, Xiao,et al."Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment".BIOMATERIALS 158(2018):44-55.
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