Oxygen-Independent Radiodynamic Therapy : Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

ACS applied materials & interfaces - (2024) vom: 16. Apr.

Sprache:

Englisch

Beteiligte Personen:

Chen, Yang [VerfasserIn]
Deng, Yong [VerfasserIn]
Li, Yiran [VerfasserIn]
Qin, Yulin [VerfasserIn]
Zhou, Zhiguo [VerfasserIn]
Yang, Hong [VerfasserIn]
Sun, Yun [VerfasserIn]

Links:

Volltext

Themen:

Charge transfer
Fenton reaction
Hypoxia
Journal Article
Radiodynamic therapy
Tumor microenvironments

Anmerkungen:

Date Revised 16.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1021/acsami.4c00793

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM371154464