Upconversion Nanoparticle Powered Microneedle Patches for Transdermal Delivery of siRNA

Microneedles (MNs) permit the delivery of nucleic acids like small interfering RNA (siRNA) through the stratum corneum and subsequently into the skin tissue. However, skin penetration is only the first step in successful implementation of siRNA therapy. These delivered siRNAs need to be resistant to enzymatic degradation, enter target cells, and escape the endosome-lysosome degradation axis. To address this challenge, this article introduces a nanoparticle-embedding MN system that contains a dissolvable hyaluronic acid (HA) matrix and mesoporous silica-coated upconversion nanoparticles (UCNPs@mSiO₂ ). The mesoporous silica (mSiO₂ ) shell is used to load and protect siRNA while the upconversion nanoparticle (UCNP) core allows the tracking of MN skin penetration and NP diffusion through upconversion luminescence imaging or optical coherence tomography (OCT) imaging. Once inserted into the skin, the HA matrix dissolves and UCNPs@mSiO₂ diffuse in the skin tissue before entering the cells for delivering the loaded genes. As a proof of concept, this system is used to deliver molecular beacons (MBs) and siRNA targeting transforming growth factor-beta type I receptor (TGF-βRI) that is potentially used for abnormal scar treatment.