Cocoon-Like Self-Degradable DNA Nanoclew for Anticancer Drug Delivery

被引:288
作者
Sun, Wujin [1 ,2 ,3 ,4 ]
Jiang, Tianyue [1 ,2 ,3 ,4 ,5 ,6 ]
Lu, Yue [1 ,2 ,3 ,4 ]
Reiff, Margaret [1 ,2 ]
Mo, Ran [1 ,2 ,3 ,4 ,5 ,6 ]
Gu, Zhen [1 ,2 ,3 ,4 ]
机构
[1] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27695 USA
[2] N Carolina State Univ, Raleigh, NC 27695 USA
[3] Univ N Carolina, UNC Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, UNC Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA
[5] China Pharmaceut Univ, Ctr Drug Discovery, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
[6] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China
关键词
RELEASE; NANOPARTICLES; NANOFLOWERS; NANOTUBES; SYSTEM;
D O I
10.1021/ja5088024
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A bioinspired cocoon-like anticancer drug delivery system consisting of a deoxyribonuclease (DNase)-degradable DNA nanoclew (NCl) embedded with an acid-responsive DNase I nanocapsule (NCa) was developed for targeted cancer treatment. The NCl was assembled from a long-chain single-stranded DNA synthesized by rolling-circle amplification (RCA). Multiple GC-pair sequences were integrated into the NCl for enhanced loading capacity of the anticancer drug doxorubicin (DOX). Meanwhile, negatively charged DNase I was encapsulated in a positively charged acid-degradable polymeric nanogel to facilitate decoration of DNase I into the NCl by electrostatic interactions. In an acidic environment, the activity of DNase I was activated through the acid-triggered shedding of the polymeric shell of the NCa, resulting in the cocoon-like self-degradation of the NCl and promoting the release of DOX for enhanced therapeutic efficacy.
引用
收藏
页码:14722 / 14725
页数:4
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