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Hyperbranched poly(beta-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer

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Pubmed体系：

收录情况： ◇ SCIE ◇ EI

作者：
Xueqin Gao[a] * ; Zhuang Jin[c] * ; Xiangyu Tan[k] * ; Chong Zhang[b] ; Chenming Zou[a] ; Wei Zhang[b] ; Jiahui Ding[b] ; Bhudev C. Das[d] ; Konstantin Severinov[e] ; Inga Isabel Hitzeroth[f] ; Priya Ranjan Debata[g] ; Dan He[h] ; Xin Ma[i] ; Xun Tian[j] ; Qinglei Gao[k] ; Jun Wu[l] ; Rui Tian[c] ; Zifeng Cui[c] ; Weiwen Fan[c] ; Zhaoyue Huang[c] ; Chen Cao[j] ; Yuxian Bao[m] ; Songwei Tan[b] ; Zheng Hu[c,k,n] ;
单位： [a]Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China [b]School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [c]Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China [d]Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Uttar Pradesh, Noida 201313, India [e]Skolkovo Institute of Science and Technology, Skolkovo, Moscow Region 143025, Russia [f]Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, South Africa [g]Department of Zoology, North Orissa University, Takatpur, Baripada, Odisha 757003, India [h]Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China [i]Department of Urology, General Hospital of People's Liberation Army, Beijing 100039, China [j]Department of Obstetrics and Gynecology, Academician expert workstation, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei, China [k]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China [l]School of Biomedical Engineering, Sun Yat-sen University, Guangzhou 510006, Guangdong, China [m]Generulor Company Bio-X Lab, Guangzhou 510006, Guangdong, China [n]Precision Medicine Institute, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
出处：
DOI： 10.1016/j.jconrel.2020.02.045
ISSN：

关键词： Cervical cancer Poly(beta-amino ester) Hyperbranched copolymer HPV CRISPR/Cas9

摘要：
Persistent high-risk HPV infection is the main factor for cervical cancer. HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(beta-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(beta-amino ester) (PBAE) and plasmids were approximately 300 nm. These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice. Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.

基金：
National Science and Technology Major Project of the Ministry of science and technology of China [2018ZX10301402]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81871473, 81761148025, 81402158]; Guangzhou Science and Technology Programme [201704020093]; National Ten Thousand Plan-Young Top Talents of China; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [17ykzd15, 19ykyjs07]; Three Big Constructions-Supercomputing Application Cultivation Projects - National Supercomputer Center In Guangzhou; Russian Foundation for Basic ResearchRussian Foundation for Basic Research (RFBR) [17-54-80078]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类 | 1 区 医学
小类 | 1 区 药学 2 区 化学综合
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药学 2 区 化学：综合
JCR分区：
出版当年[2018]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者单位： [a]Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
共同第一作者：
通讯作者：
通讯机构： [c]Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China [k]Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China [n]Precision Medicine Institute, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
推荐引用方式(GB/T 7714)：
Xueqin Gao,Zhuang Jin,Xiangyu Tan,et al.Hyperbranched poly(beta-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer[J].JOURNAL OF CONTROLLED RELEASE.2020,321:654-668.doi:10.1016/j.jconrel.2020.02.045.
APA：
Xueqin Gao,Zhuang Jin,Xiangyu Tan,Chong Zhang,Chenming Zou...&Zheng Hu.(2020).Hyperbranched poly(beta-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer.JOURNAL OF CONTROLLED RELEASE,321,
MLA：
Xueqin Gao,et al."Hyperbranched poly(beta-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer".JOURNAL OF CONTROLLED RELEASE 321.(2020):654-668

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