Rail-Guided Chitosan Nano-reorchestration of MoS₂ and Hemoglobin Enables NIR Photoelectrothermal H₂/O₂ Generation in a Pancreas-Targeted Hydrogel.

Abstract

Near-infrared (NIR)-addressable biohybrids that co-deliver thermal, ionic, and gaseous cues can protect β-cells. We report an HA hydrogel embedding chitosan (CS) nano-structurally reprogramming MoS₂/hemoglobin (HB) in which CS builds "protonic tracks"-a fixed-charge (cationic) polyelectrolyte network that routes photocharges/protons away from MoS₂ active sites, lowers interfacial resistance, and multidentately anchors MoS₂/HB to prevent aggregation and preserve HB function. Colloidal screening identifies MoS₂:CS:HB = 1:1:3, minimizing size and stabilizing ζ-potential. Under 808-nm light, the composite reaches ∼39°C (vs. ∼37°C without CS), accelerates Prussian Blue bleaching, strengthens resazurin H₂ signals, and increases dissolved O₂ (∼7.5 vs. ∼5.3 mg L^- ¹), evidencing rail-guided photocatalysis wherein photothermal elevation is tightly coupled to charge/proton transport and gas generation. In vivo, FITC-labeled formulations accumulate in the pancreas. Treatment with MoS₂/CS/HB@HA under NIR irradiation reduces blood glucose levels without inducing histological toxicity and promotes islet remodeling, as evidenced by enhanced EdU incorporation, upregulated insulin expression, an increased M2/M1 macrophage ratio, reduced ROS levels, and elevated HSP expression. Collectively, the proton-conductive pathways provided by CS transform the hydrogel into an NIR-responsive, interfacially stabilized bioreactor that integrates MoS₂-mediated photoelectrothermal transduction with HB-assisted oxygen handling. This compact, externally controllable platform demonstrates strong potential as an adjunctive strategy for diabetes management.