Cascade Reaction of "Mn2+ -Catechol" Triggered by H2 O2 to Integrate Firm Tumor Vessel Embolization and Hypoxic Response Relief.

Abstract

Transcatheter arterial embolization (TAE) therapy requires firm and long-term vessel embolization without recanalization. However, firm embolization usually leads to unanticipated hypoxic response which promotes tumor recurrence and metastasis. Herein, an injectable thermosensitive hydrogel containing catechol groups and Mn2+ (PNDM) has been developed to enhance embolization and inhibit hypoxic response utilizing augmented H2 O2 after TAE. This novel embolic agent converts H2 O2 into hydroxyl radicals via Mn2+ -dependent Fenton-like reaction, which are subsequently scavenged through a "catechol-quinone" transition to suppress hypoxic responses. Quinone structure can not only make hydrogel internal structure more compact, but also enhance hydrogel adhesion to vessel wall. In vivo experiments confirm that the rabbit renal artery can be firmly embolized for 84 days. Studies in liver VX2 tumor-bearing rabbits demonstrate that the PNDM-based TAE can promote tumor necrosis, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This strategy opens new sights in the TAE therapy for liver cancer.