Versatile Catalytic Deoxyribozyme Vehicles for Multimodal Imaging-Guided Efficient Gene Regulation and Photothermal Therapy

Catalytic deoxyribozyme has great potential for gene regulation, but the poor efficiency of the cleavage of mRNA and the lack of versatile DNAzyme vehicles remain big challenges for potent gene therapy. By the rational designing of a diverse vehicle of polydopamine-Mn2+ nanoparticles (MnPDA), we demonstrate that MnPDA has integrated functions as an effective DNAzyme delivery vector, a self-generation source of DNAzyme cofactor for catalytic mRNA cleavage, and an inherent therapeutic photothermal agent as well as contrast agent for photoacoustic and magnetic resonance imaging. Specifically, the DNAzyme-MnPDA nanosystem protects catalytic deoxyribozyme from degradation and enhances cellular uptake efficiency. In the presence of intracellular glutathione, the nanoparticles are able to in situ generate free Mn2+ as a cofactor of DNAzyme to effectively trigger the catalytic cleavage of mRNA for gene silencing. In addition, the nanosystem shows high photothermal conversion efficiency and excellent stability against photothermal processing and degradation in complex environments. Unlike previous DNAzyme delivery vehicles, this vehicle exhibits diverse functionalities for potent gene regulation, allowing multimodal imaging-guided synergetic gene regulation and photothermal therapy both in vitro and in vivo.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

ACS nano - 12(2018), 12 vom: 26. Dez., Seite 12888-12901

Sprache:

Englisch

Beteiligte Personen:

Feng, Jie [VerfasserIn]
Xu, Zhen [VerfasserIn]
Liu, Feng [VerfasserIn]
Zhao, Yun [VerfasserIn]
Yu, Wenqian [VerfasserIn]
Pan, Min [VerfasserIn]
Wang, Fuan [VerfasserIn]
Liu, Xiaoqing [VerfasserIn]

Links:

Volltext

Themen:

42Z2K6ZL8P
Antineoplastic Agents
Contrast Media
DNA, Catalytic
DNAzyme
Deoxyribozyme
Gene therapy
Indoles
Journal Article
Manganese
Multimodal imaging
Photothermal therapy
Polydopamine
Polymers
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.10.2019

Date Revised 23.10.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acsnano.8b08101

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM291704948