Ruthenium Nanozyme@Magnesium silicate nanosheets encapsuled in microneedle patches promote repair of radiation-induced skin defects by remodeling pathological environment

Abstract

Radiotherapy induced skin defect (RISD) is a severe radiotherapy complication with persistent oxidative stress and recurrent excessive reactive oxygen species (ROS), impeding normal tissue repair processes. Nevertheless, the lack of a standardized animal model severely hinders the progress of related research work. We develop a novel strategy for repairing the RISD microenvironment, which combines initial ROS clearance, subsequent inhibition of ROS production and the repair of proliferation related cell pathways/functions. As a proof of concept, a composite microneedle (MN) patch comprising γ-polyglutamic acid as the base and ruthenium (Ru) clusters modified magnesium silicate nanosheets (MSR NSs) as the enzyme-like component is prepared. The Ru clusters have excellent ROS scavenging ability and help activate the peroxisome proliferators activated receptor signaling pathway confirmed by the sequencing analysis while the magnesium silicate is degraded under physiological conditions to release magnesium ions and silicate ions, enhancing cell proliferation, migration, and angiogenesis ability. The radiation induced skin defect animal model is established to evaluate the RISD repair efficacy of our MSR@MN patch in comparison with γPGA-MSR ointment and commercial product Orgotein. The results show that our MSR@MN patch effectively improves the pathological microenvironment of abnormal ROS accumulation, reduces inflammatory response and promotes mature angiogenesis and tissue remodeling.