Cascade Reaction of “Mn²⁺‐Catechol” Triggered by H₂O₂ 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 Mn 2+ (PNDM) has been developed to enhance embolization and inhibit hypoxic response utilizing augmented H 2 O 2 after TAE. This novel embolic agent converts H 2 O 2 into hydroxyl radicals via Mn 2+ -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.

Shape Self-Adaptive Liquid Embolic Agent for Ultrafast and Durable Vascular Embolization

“…The setup consisted of a microfluidic syringe pump in the upstream, a pressure testing device called the RM6240 Bio-Signal Acquisition and Processing System in the middle, and an infusion tube filled with anticoagulated blood in the downstream (Figure e). As shown in Figure f, when Lipiodol was used to embolize the catheter, the determined pressure quickly increased to 15 kPa in a short time and then sharply decreased, indicating the failure of durable embolization and the occurrence of recanalization. − In contrast, the pressure in the PAA-LDH@PEG200 group quickly increased to 40 kPa and showed a rising trend for a long time, suggesting the strong and durable embolization effect of PAA-LDH@PEG200 to the catheter.…”

Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy

“…S2). This enhanced Mn 2+ release can be attributed to the competitive coordination of Mn 2+ with –SH moieties within GSH, along with the –SH-mediated reaction with TA [ 43 ]. To validate this hypothesis, the consumption of GSH was quantified, revealing a direct correlation between NPs concentration and GSH utilization ( Fig.…”

Efficacy, mechanism, and safety of melatonin‐loaded on thermosensitive nanogels for rabbit VX2 tumor embolization: A novel design

“…In this study, embolism could damage liver and kidney functions, which was similar to the results reported by previous studies. 23,25,26 The liver and kidney functions of rabbits were most damaged on the third day after embolization (PIB and PIB-M groups) but gradually recovered on the seventh day. Therefore, melatonin administration in vivo did not increase the side effects in rabbits after treatment.…”

“…The embolization procedure was reported by our previous studies [25][26][27] and were presented in the Supporting Information Materials.…”