典型文献
Apoptosis-enhanced ferroptosis therapy of pancreatic carcinoma through PAMAM dendrimer-iron(Ⅲ)complex-based plasmid delivery
文献摘要：
The development of promising strategies to improve the treatment efficacy of pancreatic carcinoma still remains to be a challenging task.We report here the development of a new dendrimer-based nanomedicine formulation to tackle pancreatic carcinoma through apoptosis-enhanced ferroptosis therapy.In this article,G5 dendrimers were partially modified with a Fe(Ⅲ)chelator hydroxyquinoline-2-carboxylic acid(8-HQC)on their periphery,entrapped with gold nanoparticles(Au NPs)within their internal cavities,and chelated with Fe(Ⅲ).The thus created dendrimer-entrapped Au NPs(Fe-Au DENP-HQC)with an Au core size of 1.9 nm and 20.0 Fe(Ⅲ)ions complexed per dendrimer are stable,have a pH-dependent Fe(Ⅲ)release profile,and can generate reactive oxygen species under the tumor microenvironment(TME)and effectively compact plasmid DNA encoding p53 protein to form polyplexes with a hydrodynamic size of 143.9 nm and a surface potential of 33.6 mV.We show that cancer cells treated with the created Fe-Au DENP-HQC/p53 polyplexes can be more significantly inhibited through vector-mediated chemodynamic therapy(CDT)effect via Fe(Ⅲ)-induced Fenton reaction and the p53 gene delivery-boosted cell apoptosis and oxidative stress in the TME than single-mode CDT and gene therapy.Further investigations using a xenografted tumor model validated the effectiveness of apoptosis-enhanced ferropotosis therapy through the downregulation of GPX-4 and SLC7A11 proteins,upregulation of p53 and PTEN proteins,as well as histological examinations.Meanwhile,the dendrimer nanoplatform enabled tumor fluorescence imaging through gene delivery-mediated enhanced green fluorescent protein expression.The Fe(Ⅲ)-complexed dendrimer vector system may be developed as a promising theranostic nanoplatform for ferroptosis or ferroptosis-based combination therapy of other cancer types.
文献关键词：
中图分类号：
作者姓名：
Wenjing Ma;Yue Gao;Zhijun Ouyang;Yu Fan;Hongwei Yu;Mengsi Zhan;Han Wang;Xiangyang Shi;Mingwu Shen
作者机构：
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine,College of Chemistry,Chemical Engineering and Biotechnology,Donghua University,Shanghai 201620,China;Department of Radiology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
文献出处：
引用格式：
[1]Wenjing Ma;Yue Gao;Zhijun Ouyang;Yu Fan;Hongwei Yu;Mengsi Zhan;Han Wang;Xiangyang Shi;Mingwu Shen-.Apoptosis-enhanced ferroptosis therapy of pancreatic carcinoma through PAMAM dendrimer-iron(Ⅲ)complex-based plasmid delivery)[J].中国科学:化学（英文版）,2022(04):778-788
A类：
DENP,polyplexes,ferropotosis
B类：
Apoptosis,enhanced,ferroptosis,therapy,pancreatic,carcinoma,through,PAMAM,plasmid,delivery,development,promising,strategies,improve,treatment,efficacy,still,remains,be,challenging,task,We,report,here,new,nanomedicine,formulation,tackle,apoptosis,In,this,G5,dendrimers,were,partially,modified,chelator,hydroxyquinoline,carboxylic,acid,HQC,their,periphery,entrapped,gold,nanoparticles,Au,NPs,within,internal,cavities,chelated,thus,created,core,size,complexed,are,stable,have,dependent,release,profile,generate,reactive,oxygen,species,under,tumor,microenvironment,TME,effectively,compact,encoding,p53,hydrodynamic,surface,potential,mV,show,that,cancer,cells,treated,more,significantly,inhibited,vector,mediated,chemodynamic,CDT,via,induced,Fenton,reaction,boosted,oxidative,stress,than,single,Further,investigations,using,xenografted,model,validated,effectiveness,downregulation,GPX,SLC7A11,proteins,upregulation,PTEN,well,histological,examinations,Meanwhile,nanoplatform,enabled,fluorescence,imaging,green,fluorescent,expression,system,may,developed,theranostic,combination,other,types
AB值：
0.53118
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