Cyclodextrin-engineered bioinspired nanozyme microneedle for adaptive theranostic regulation of hyperuricemia and gout.

Engineering cyclodextrin-based materials enabling real-time diagnosis and on-demand therapy is highly desirable for hyperuricemia and gout management. Here, we design a novel cyclodextrin-engineered bioinspired nanozyme (T-CD/Pt), and integrate it into a bi-regional microneedle (TP-MNs). Coupled with a biowaste-derived coffee ground photothermal film (CPS-F), the resulting CPS-F/TP-MNs platform enables localized hyperthermia and significantly enhances nanozyme catalytic activity. In T-CD/Pt, the cyclodextrin cavities function as biomimetic substrate-binding pockets, enabling selective enrichment of uric acid (UA) at the catalytic interface, whereas confined ultrasmall Pt sites serve as catalytic centers responsible for UA degradation. This bioinspired configuration establishes a coupled binding-catalysis microenvironment, rendering T-CD/Pt superior to natural uricase and conventional nanozyme design in UA degradation, dual-mode UA detection, ROS elimination, and monosodium urate crystal (MSU) inhibition/dissolution. In vitro, T-CD/Pt enhances cell viability and suppresses inflammatory cytokine expression in MSU-damaged cell models. In vivo results demonstrate that the TP-MNs normalize serum UA levels within 10 h and allow real-time, noninvasive UA monitoring in hyperuricemia mice, while NIR activation further mitigates joint edema and tissue inflammation in gout mice. This work establishes a concept-driven strategy for integrating bioinspired cyclodextrin nanozymes with a microneedle platform, expanding the potential of cyclodextrin-based materials for adaptive theranostic systems.