Inflammatory microenvironment-triggered oral mucositis treatment by guanosine microneedles
Oral mucositis (OM) is a debilitating complication of cancer therapy, characterized by severe pain, mucosal barrier breakdown, and infection risk. Current hydrogel-based topical systems suffer from poor transmucosal permeation and lack of inflammatory microenvironment-triggered drug release. Here, we report a supramolecular strategy for designing guanosine-fibril hydrogels and derived microneedle patches. Tavaborole (Ta), crisaborole (Cr), and strontium (Sr2+) ions serve dual roles as structural building blocks and biofunctional agents. Unlike conventional G4·K+ fibrils, the unique G4·Sr2+-Ta/Cr fibrils incorporate Ta/Cr via boronic ester bonds on guanosine and Sr2+ through G-quartet cation recognition. This design mechanically reinforces the hydrogel through additional hydrophobic interactions and ion-pair recognition, while synergistically providing antimicrobial/anti-inflammatory effects (Ta/Cr), pro-angiogenic activity (Sr2+), and reactive oxygen species (ROS) scavenging (guanosine). The optimized gelation process enables fabrication of microneedle patches with pseudomembrane-penetrating capability and ROS-triggered drug release via boronic ester hydrolysis. In vivo mouse experiments confirm efficacy in controlling OM-associated inflammation, modulating oral microbiota homeostasis, and promoting angiogenesis at ulcer sites. This work demonstrates multifunctional integration via hierarchical structural design, extending guanosine supramolecular assemblies into bioactive platforms for OM treatment.