Self-immolative nanosensitizer for glutathione depletion- assisted sonodynamic therapy.
Theranostics
; 12(17): 7465-7475, 2022.
Article
in En
| MEDLINE
| ID: mdl-36438485
ABSTRACT
Background:
Despite remarkable advances in sonodynamic therapy (SDT) of cancer, the low reactive oxygen species (ROS) quantum yield of the sonosensitizer remains a critical concern in glutathione (GSH)-overexpressing cancer cells.Methods:
For enhanced SDT, we report hydrophilized self-immolative polymer (SIP)-decorated TiO2 nanoparticles (HSIPT-NPs) to achieve on-demand GSH depletion and ROS generation.Results:
Upon intracellular delivery of HSIPT-NPs into hydrogen peroxide-rich cancer cells, SIP is degraded through electron transfer to produce GSH-depleting quinone methide, reprogramming GSH high cancer cells into GSH low phenotype. In the presence of ultrasound, compared to conventional TiO2 NPs, HSIPT-NPs induce significantly higher oxidative stress to cancer cells by incapacitating their antioxidant effects. SDT with HSIPT-NPs effectively inhibit tumor growth in mice via the synergistic effects of GSH depletion and ROS generation.Conclusion:
On the basis of their ability to reprogram cancer cells, HSIPT-NPs offer considerable potential as a nanosensitizer for enhanced SDT.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanoparticles
/
Neoplasms
Limits:
Animals
Language:
En
Journal:
Theranostics
Year:
2022
Document type:
Article
Publication country:
AU
/
AUSTRALIA
/
AUSTRÁLIA