In vitro 3D malignant melanoma model for the evaluation of hypericin-loaded oil-in-water microemulsion in photodynamic therapy

Advances in biomimetic three-dimensional (3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional (2D) cell culture. Gelatin methacryloyl (GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on GelMA was fabricated to evaluate the efficiency of hypericin (Hy)-loaded microemulsion (ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% GelMA and the co-culture of B16F10 and Balb/c 3T3 cells, followed by crosslinking using violet light (403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation (about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility (about 2.5-fold) than those in 2D culture. These findings indicate that the developed MEs are potential delivery carriers for Hy; furthermore, GelMA hydrogel-based modeling in polydimethylsiloxane (PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.

Automated summary

Advances in biomimetic three-dimensional melanoma models have great potential for drug screening and disease modeling. In this study, a GelMA-based 3D melanoma model using microemulsion was developed for evaluating the effectiveness of photodynamic therapy. The results showed that microemulsion loaded with hypericin exhibited higher phototoxicity and cell accumulation compared to free hypericin, and the cells cultured in the 3D system displayed lower susceptibility to the drug.