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Hypoxia‐Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild‐Photothermal Therapy
- Source :
- Angewandte Chemie. 133:21370-21374
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is usually associated with undesirable damage to healthy organs nearby due to the high temperatures (>50 °C) available for tumor ablation. Low-temperature PTT would therefore have tremendous value for clinical application. Here, we construct a hypoxia-responsive gold nanorods (AuNRs)-based nanocomposite of CRISPR-Cas9 for mild-photothermal therapy via tumor-targeted gene editing. AuNRs are modified with azobenzene-4,4'-dicarboxylic acid (p-AZO) to achieve on-demand release of CRISPR-Cas9 using hypoxia-responsive azo bonds. In the hypoxic tumor microenvironment, the azo groups of the hypoxia-activated CRISPR-Cas9 nanosystem based on gold nanorods (APACPs) are selectively reduced by the overexpression of reductases, leading to the release of Cas9 and subsequent gene editing. Owing to the knockout of HSP90α for reducing the thermal resistance of cancer cells, highly effective tumor ablation both in vitro and in vivo was achieved with APACPs under mild PTT.
- Subjects :
- Cell Survival
Infrared Rays
Photothermal Therapy
Metal Nanoparticles
Antineoplastic Agents
Catalysis
Genome editing
In vivo
medicine
Humans
Dicarboxylic Acids
Particle Size
Cell Proliferation
Gene Editing
Hypoxic tumor
Chemistry
General Chemistry
General Medicine
Hypoxia (medical)
Photothermal therapy
In vitro
Cell Hypoxia
A549 Cells
Cancer cell
Biophysics
Nanorod
Gold
medicine.symptom
CRISPR-Cas Systems
Drug Screening Assays, Antitumor
Azo Compounds
Subjects
Details
- ISSN :
- 15213757 and 00448249
- Volume :
- 133
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie
- Accession number :
- edsair.doi.dedup.....9a0ec7d29a32d329510f051f4ec1a366