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

• Published in: Journal of the American Chemical Society Vol. 136; no. 42; pp. 14722 - 14725
• Main Authors: Sun, Wujin, Jiang, Tianyue, Lu, Yue, Reiff, Margaret, Mo, Ran, Gu, Zhen
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.10.2014
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Communication; deoxyribonuclease I; Deoxyribonucleases - metabolism; DNA - chemistry; DNA - metabolism; doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Carriers - metabolism; drug delivery systems; Drug Liberation; electrostatic interactions; Humans; MCF-7 Cells; Models, Molecular; Molecular Conformation; Nanoparticles - chemistry; neoplasms; single-stranded DNA
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja5088024

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.