Leveraging Radiation-triggered Metal Prodrug Activation Through Nanosurface Energy Transfer for Directed Radio-chemo-immunotherapy.
Angew Chem Int Ed Engl
; 63(10): e202317943, 2024 Mar 04.
Article
en En
| MEDLINE
| ID: mdl-38078895
ABSTRACT
Metal-based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation-triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core-shell nanoplatform (Ru-GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)-containing organic-inorganic hybrid coatings. Upon X-ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation-excited Ru-GNCs to the Ru-containing hybrid layer. In contrast to the traditional radiation-triggered activation of prodrugs, such an NSET-based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru-GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru-GNC-directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death-ligand 1 (PD-L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation-triggered nanoplatforms for metal-prodrug-mediated cancer treatment in an efficient and controllable manner.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Profármacos
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2024
Tipo del documento:
Article
País de afiliación:
China