Metal-free polymer nano-photosensitizer actuates ferroptosis in starved cancer.
Biomaterials
; 292: 121944, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36495801
ABSTRACT
The microenvironment in solid tumors drives the fate of cancer cells to ferroptosis, yet the underlying mechanism remains incompletely understood. Herein, we report a metal-free polymer photosensitizer (BDPB) as a new type ferroptosis inducer of starved cancer cells. The polymer consists of boron difluoride dipyrromethene dye as the photosensitizing unit and diisopropyl-ethyl amine as the electron-donating unit. Ultrafast spectroscopy and electron spin resonance mechanistically revealed the prolonged charge-separation process in BDPB, enabling complex-I like one-electron transfer effect to produce O2â-. Unexpectedly, the O2â--generating BDPB nanoparticles (NPs) served to deactivate the AMPK-mTOR signaling pathway in normal-state cancer cells to initiate cell repair activity and survive low-dose phototherapy. However, for cancer cells in a starved state, BDPB NPs triggered glutathione peroxidase 4 downregulation, lipid peroxides accumulation, and death to cancer cells, which was identified as ferroptosis but not apoptosis, necroptosis, or autosis. The application of BDPB NPs sheds new light on the design of individualized ferroptosis inducers for combating cancer progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ferroptosis
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Biomaterials
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS