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

作　　者：Hui LMa Wanlu Li Mian Wang Laudemir C.Varanda Janice R.Perussi Y.Shrike Zhang Emanuel Carrilho 

机构地区：[1]Instituto de Química de São Carlos,Universidade de São Paulo,USP,Av.Trabalhador São-carlense,São Carlos,SP 13566-590,Brazil [2]Instituto Nacional de Ciência e Tecnologia de Bioanalítica,INCTBio,Campinas,SP 13083-970,Brazil [3]Division of Engineering in Medicine,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Cambridge,MA 02139,USA

出　　处：《Bio-Design and Manufacturing》2022年第4期660-673,共14页生物设计与制造（英文）

基　　金：supported in part by the FAPESPINCTBio (Process 2014/50867-3);FAPESP-CEPOF (2013/072761);support by the Brigham Research Institute;LCV thanks FAPESP for financial support (Process 2013/01284-2)。

摘　　要：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 Gel MA 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% Gel MA 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, Gel MA 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.

关 键 词：Malignant melanoma 3D cell culture HYPERICIN MICROEMULSION Photodynamic therapy 

分 类 号：R739.5[医药卫生—肿瘤]