Advanced science (Weinheim, Baden-Wurttemberg, Germany)Sep 21, 2026

Targeted Delivery to Skin Layers Using Adjustable Nanoparticle and Gel-Coated Microneedles

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 22, 2026

Abstract

The threaded microneedle-mRNA platform reduced dermal senescence by targeting specific skin layers.

Layer-specific targets in skin fibrosis were identified using spatial transcriptomics and clinical validation.
The system employs a fast-releasing hydrogel to deliver a SIRT1 agonist to the dermis.
Helical grooves in the microneedle design enable targeted delivery of PGC1α mRNA-LNPs to subcutaneous adipose tissue.
In a bleomycin-induced mouse model of fibrosis, the microneedle platform restored subcutaneous adipose architecture.
Overall fibrosis and extracellular matrix deposition were attenuated in the treated mice.

Simplified

Skin diseases exhibit hierarchical pathological remodeling across the epidermis, dermis, and subcutaneous tissue. However, current therapies lack precise and controllable layer-specific intervention. Here, we present a threaded microneedle-mRNA platform enabling stratified, targeted delivery. Guided by spatial transcriptomics and clinical validation, we identified layer-specific targets in skin fibrosis. Optimized lipid nanoparticles (LNPs) were integrated into a microneedle design featuring a fast-releasing superficial hydrogel that delivers a SIRT1 agonist to mitigate dermal fibroblast senescence, and helical grooves that directionally deposit PGC1α mRNA-LNPs into subcutaneous adipose during rotational insertion for in situ expression and reversal of adipocyte fibrotic phenotypes. In bleomycin-induced murine fibrosis, the system reduced dermal senescence and ECM deposition, restored subcutaneous adipose architecture, and attenuated overall fibrosis. This layer-specific microneedle-mRNA strategy offers a precise therapeutic pathway for complex skin diseases.