Local delivery of celecoxib/indocyanine green-loaded nanomodulators for combinational photothermal/photodynamic/anti-cyclooxygenase-2 therapy of oral leukoplakia

Oral leukoplakia (OLK) is a typical precancerous lesion in oral clinics. Current treatments, including topical drugs and photodynamic therapy (PDT), have limitations such as complex procedures, suboptimal efficacy, high recurrence rates, and low permeability. The microneedle patches solve the problem of low permeability as a painless local delivery method. In this study, we developed double-layered dissolving microneedle patches loaded with novel multifunctional nanoparticles (ICM NPs) for treating OLK. The ICM NPs involve mesoporous polydopamine for photothermal therapy (PTT), indocyanine green for PDT, and celecoxib to regulate OLK progression. Furthermore, ICM NPs exhibited excellent photothermal properties under 808 nm laser irradiation, efficient reactive oxygen species-generating, and strong anti-cyclooxygenase (COX)-2 abilities. The patch effectively inhibited OLK cancerization in oral precancer animal models through the synergistic action of photothermal, photodynamic, and anti-COX-2 and had no apparent toxicity in vivo. Our study combines the minimally invasive and deep penetration capabilities of microneedles with PDT/PTT and COX-2 inhibitors, which is expected to be a new choice for the treatment of OPMDs.