Abstract

DNAzyme-based gene silencing therapies are promising candidates for the treatment of inflammatory bowel disease (IBD). However, DNAzyme’s unique substrate, structural instability, and conditional catalytic mechanism necessitate delivery systems enabling concurrent integration of precision (gene silencing surveillance), durability (degradation resistance), and efficacy (sustained catalytic output). Herein, we propose a smart photoacoustic imaging (PAI)-guided nanozyme-DNAzyme platform for combinational catalytic therapy (NDCT) of IBD by introducing the antioxidant iridium nanozyme (IrNZ) as a protector for DNAzyme and in-situ amplifier of PAI signal. The integrated IrNZ enables PAI-guided self-monitoring of the combinational catalytic processes with deep tissue penetration through the microbubble-based inertial cavitation mechanism, thereby improving the accuracy for IBD treatment. Furthermore, benefiting from the IrNZ-enabled ROS elimination, the DNAzyme drug displays excellent self-protective capacity and anti-inflammatory activity in the deleterious oxidative inflammatory microenvironment. Besides, the self-sufficient Zn 2+ metal cofactors for DNAzyme by NDCT further improves their gene-silencing performance. Hence, the NDCT establishes a self-traceable, self-protective, and self-sufficient (3S) strategy for highly accurate, durable and efficient nanozyme-DNAzyme combinational catalytic therapy of IBD. A smart nanozyme-DNAzyme combinational catalytic platform NDCT is proposed for concurrent integration of precision (gene silencing surveillance), durability (degradation resistance), and efficacy (sustained catalytic output). Benefiting from the self-traceable therapeutic monitoring, nanozyme-enabled self-protection of DNAzyme cargos, and self-sufficient Zn 2+ cofactors, the NDCT demonstrates robust therapeutic performance, offering strong potential for highly accurate, durable and efficient IBD therapy. Download: Download high-res image (155KB) Download: Downl