Polydopamine/IR820 nanoparticles as topical phototheranostics for inhibiting psoriasiform lesions through dual photothermal and photodynamic treatments

Dual photothermal and photodynamic therapy (PTT and PDT) is an attractive approach that generates a synergistic effect for inhibiting keratinocyte hyperproliferation in the treatment of psoriasis. Here, we developed phototheranostic nanocarriers capable of producing hyperthermia and reactive oxygen species (ROS) in response to near-infrared (NIR) illumination. To this end, IR820 with photothermal and photodynamic features was embedded in nano-sized polydopamine (PDA) acting as a PTT agent. A comprehensive characterization of the PDA/IR820 nanosystem was performed according to its morphology, size, zeta potential, UV absorbance, and heat generation. Its therapeutic efficacy was assessed by a keratinocyte-based study and using an imiquimod (IMQ)-stimulated psoriasiform murine model. PDA/IR820 nanoparticles were facilely internalized into keratinocytes and mainly resided in lysosomes. Upon irradiation with NIR light, ROS were generated inside the keratinocytes to cause a photodynamic effect. The live/dead cell assay and cytotoxicity assay demonstrated that PDA and IR820 acted as effective photoabsorbers to induce keratinocyte death. The highest cytotoxic effect was detected in the group of NIR-irradiated PDA/IR820 nanoparticles, which killed 52% of keratinocytes. The nanosystem acted through the caspase and poly ADP-ribose polymerase (PARP) pathways to induce keratinocyte apoptosis. In vitro and in vivo skin permeation indicated the selective accumulation of the topically applied PDA/IR820 nanoparticles within psoriasiform skin, suggesting their skin-targeting capability. The combination of PDA/IR820 nanoparticles and NIR irradiation increased the skin temperature by 11.7 degrees C. PTT/PDT eliminated psoriasiform plaques in mice by decreasing hyperplasia, inhibiting cytokine overexpression, and recovering the barrier function. The epidermal thickness of the IMQ-treated skin was reduced from 134 to 34 mu m by the nanocarriers plus NIR. The IR820 nanoparticles were largely deposited on the inflamed areas of psoriasiform lesions for monitoring the severity of inflammation. The image-guided phototheranostic nanoparticles showed their potential for applications in psoriasis management via noninvasive topical administration.