Melanoma Biohacking by Micellar Formulation for Topical Application: Validation in Multicellular Bioprinted Skin

• Grant number: 25/00313-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Carmen Veríssima Ferreira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Bruna Alice Gomes de Melo ; Marcos Akira d'Ávila
• Associated scholarship(s): 25/12280-5 - Impact of Micellar Riboflavin in Normal Skin Cells: Melanocytes and Fibroblasts, BP.IC

Abstract

Melanomas are the most aggressive skin tumors, with poor response to therapy, and therefore responsible for more than 80% of deaths associated with skin neoplasms. The treatment of melanoma is a chalenge due to its high resistance and aggressiveness, which often requires therapeutic protocols that can cause significant adverse effects, representing an additional obstacle to therapeutic management. In this context, in recent years, we have identified molecular mediators associated with melanoma migration, adhesion, and survival, which are turned off by riboflavin photoproducts (FPRF). The antitumor effect of FPRF has been demonstrated in models of increasing complexity: 2D and 3D cell cultures (spheroids and organoids), and in vivo (mouse pulmonary metastasis model). Given the promising effect of FPRFs, we developed formulations based on Pluronic for topical administration, containing these riboflavin derivatives. Nanocarrier systems based on gel copolymers, such as Pluronic, have remained in the spotlight due to their low cost and their ability to significantly increase the bioavailability of the compounds they carry out. The use of Pluronic for nanodelivery of FPRF appears to be a promising topical formulation, already validated in animal model (mouse pulmonary metastasis). Therefore, our current focus is to determine whether this formulation is also effective on artificial human skin (containing melanoma foci) prepared from normal cells (keratinocytes, fibroblasts, and melanocytes) and melanoma cell lines (BRAF and NRAS). It is important to highlight that recent studies emphasize the importance of screening drug candidates in more complex experimental models that can more accurately simulate the tumor microenvironment and the various cellular interactions that occur in vivo, such as multicellular 3D cultures. Therefore, this project could provide the population with access to a new therapeutic option. Furthermore, the establishment of an artificial skin model that does not rely on skin derived from plastic surgeries (samples from volunteers) for preparation will enable more research groups to use the model for different applications. (AU)