Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy

被引:20
作者
Li, Jin [1 ]
Qiu, Liping [1 ]
Xie, Sitao [1 ]
Zhang, Jing [1 ]
Zhang, Liqin [1 ,2 ,3 ,4 ]
Liu, Honglin [1 ]
Li, Juan [5 ]
Zhang, Xiaobing [1 ]
Tan, Weihong [1 ,2 ,3 ,4 ]
机构
[1] Hunan Univ, Coll Life Sci, Aptamer Engn Ctr Hunan Prov,Coll Chem & Chem Engn, Mol Sci & Biomed Lab,State Key Lab Chemo Biosensi, Changsha 410082, Hunan, Peoples R China
[2] Univ Florida, Dept Chem, Ctr Res Bio Nano Interface, Gainesville, FL 32611 USA
[3] Univ Florida, UF Genet Inst, Hlth Canc Ctr, Dept Physiol & Funct Genom, Gainesville, FL 32611 USA
[4] Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA
[5] Fuzhou Univ, Coll Chem, Key Lab Analyt Sci Food Safety & Biol, Minist Educ, Fuzhou 350116, Fujian, Peoples R China
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
aptamer; drug delivery; personalized medicine; antisense oligonucleotides; DRUG-DELIVERY; DNA NANOTECHNOLOGY; INTRACELLULAR DRUG; CONTROLLED-RELEASE; NANOCARRIERS; INHIBITION; LIPOSOMES; MEDICINE; PROGRESS; FUTURE;
D O I
10.1007/s11426-017-9176-3
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411, and a replaceable anti-biomarker probe (ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.
引用
收藏
页码:497 / 504
页数:8
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