Transdermal hyaluronate/cationic solid lipid nanoparticle/siRNA complex for the treatment of skin cancer

Lipid nanoparticles (LNPs) are widely recognized for their potential in drug delivery. However, they exhibit significant limitations in stability and targeting. In this study, we designed a target-specific siRNA delivery system by coating hyaluronate (HA) onto cationic solid lipid nanoparticles (CSLNs). The angiogenesis-inhibiting siVEGF formed a stable nanoscale complex for the targeted delivery to skin cancer tissue. The nucleic acid drug in the HA/CSLN/siVEGF complex was electrostatically coated on the surface of CSLN, enabling high drug loading capacity. Moreover, HA appeared to serve a dual purpose in this design by targeting to cancer cells and facilitating effective transdermal delivery. The optimized HA/CSLN/siVEGF complex resulted in facilitated transdermal delivery, effective tumor targeting, and significantly reduced VEGF mRNA levels, leading to tumor growth inhibition. Taken together, the HA/CSLN complex would be successfully harnessed as a transdermal target-specific delivery carrier of siRNA for cancer therapy.