Disease-Adaptive ROS-Responsive MOF-818 Nanozyme Microneedles for Localized Catalytic Antioxidant Therapy of Psoriasis

Abstract Psoriasis is a chronic inflammatory skin disease characterized by excessive reactive oxygen species (ROS) accumulation, persistent inflammation, and abnormal keratinocyte proliferation. Although antioxidant-based strategies have shown therapeutic potential, their efficacy is often limited by the impaired permeability of psoriatic skin and the lack of disease-responsive drug release. Herein, we developed a disease-adaptive ROS-responsive nanozyme microneedle platform for localized catalytic antioxidant therapy of psoriasis. MOF-818 nanozymes exhibited intrinsic superoxide dismutase (SOD)- and catalase (CAT)-like activities, enabling catalytic scavenging of superoxide and hydrogen peroxide. The nanozymes were incorporated into a hydrogel microneedle composed of phenylboronic acid-modified hyaluronic acid (HP) and epigallocatechin gallate (EGCG) through dynamic boronate ester bonds. Under oxidative conditions, ROS-triggered cleavage of these dynamic bonds accelerated the release of MOF-818 and EGCG, thereby coupling antioxidant delivery to the local oxidative microenvironment. The resulting microneedles exhibited sufficient mechanical strength for skin penetration and showed ROS-responsive release behavior in vitro. In an imiquimod-induced psoriasis mouse model, MOF-818/EGCG/HP microneedles significantly reduced ear thickness, epidermal hyperplasia, and spleen index. Moreover, treatment decreased the expression of the pro-inflammatory cytokines TNF-α and IL-6, suppressed keratinocyte proliferation, and reduced the infiltration of CD3 + T lymphocytes and CD68 + macrophages in psoriatic lesions. These findings demonstrate that integrating catalytic nanozyme activity with ROS-responsive microneedle delivery enables localized regulation of the oxidative and inflammatory microenvironment, providing a disease-adaptive biomaterial strategy for psoriasis therapy.