CytoDirect : A Nucleic Acid Nanodevice for Specific and Efficient Delivery of Functional Payloads to the Cytoplasm

Direct and efficient delivery of functional payloads such as chemotherapy drugs, siRNA, or small-molecule inhibitors into the cytoplasm, bypassing the endo/lysosomal trapping, is a challenging task for intracellular medicine. Here, we take advantage of the programmability of DNA nanotechnology to develop a DNA nanodevice called CytoDirect, which incorporates disulfide units and human epidermal growth factor receptor 2 (HER2) affibodies into a DNA origami nanostructure, enabling rapid cytosolic uptake into targeted cancer cells and deep tissue penetration. We further demonstrated that therapeutic oligonucleotides and small-molecule chemotherapy drugs can be easily delivered by CytoDirect and showed notable effects on gene knockdown and cell apoptosis, respectively. This study demonstrates the synergistic effect of disulfide and HER2 affibody modifications on the rapid cytosolic delivery of DNA origami and its payloads to targeted cells and deep tissues, thereby expanding the delivery capabilities of DNA nanostructures in a new direction for disease treatment.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:145

Enthalten in:

Journal of the American Chemical Society - 145(2023), 50 vom: 20. Dez., Seite 27336-27347

Sprache:

Englisch

Beteiligte Personen:

Yu, Lu [VerfasserIn]
Xu, Yang [VerfasserIn]
Al-Amin, Md [VerfasserIn]
Jiang, Shuoxing [VerfasserIn]
Sample, Matthew [VerfasserIn]
Prasad, Abhay [VerfasserIn]
Stephanopoulos, Nicholas [VerfasserIn]
Šulc, Petr [VerfasserIn]
Yan, Hao [VerfasserIn]

Links:

Volltext

Themen:

9007-49-2
DNA
Disulfides
Journal Article
Nucleic Acids
Research Support, N.I.H., Extramural

Anmerkungen:

Date Completed 21.12.2023

Date Revised 14.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/jacs.3c07491

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365468355