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

Author(s)

Ma, Hui L. ; Li, Wanlu ; Wang, Mian ; Varanda, Laudemir C. ; Perussi, Janice R. ; Zhang, Y. Shrike ; Carrilho, Emanuel

• Document type: Journal article
• Source: BIO-DESIGN AND MANUFACTURING; v. 5, n. 4, p. 14-pg., 2022-07-23.

Abstract

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. (AU)

• FAPESP's process: 13/01284-2 - Theranostic nanoparticles based in superparamagnetic iron oxide for skin cancer therapy by magnetic hyperthermia
• Grantee: Laudemir Carlos Varanda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC