Nanoparticle-Based Phototherapies: Enhancing Photothermal and Photodynamic Treatment Strategies For Melanoma

• Grant number: 25/02447-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Pedro Henrique Benites Aoki
• Grantee: Pedro Henrique Benites Aoki
• Principal researcher abroad: Christelle Prinz
• Institution abroad: Lund University, Lund, Sweden
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated research grant: 22/02189-2 - Plasmonic nanostructures for synergistic photodynamic (PDT) and photothermal (PTT) therapy of cancer cells, AP.PNGP.PI

Abstract

Cancer remains a leading global health concern, significantly affecting millions worldwide. Among the various types, skin cancer is one of the most frequently diagnosed, with melanoma representing a substantial subset of cases. Despite its relatively lower incidence, melanoma is highly lethal, with a mortality-to-incidence ratio of 17.6%. Conventional cancer treatments often have limitations, including severe side effects and drug resistance, demanding alternative therapeutic approaches such as light-based therapies. Photodynamic therapy (PDT) utilizes light-activated photosensitizers (PS) that generate reactive oxygen species (ROS) in the presence of oxygen, selectively inducing cytotoxicity in tumor cells. Conversely, photothermal therapy (PTT) is oxygen-independent, relying on photothermal agents that convert light into heat, effectively destroying cancer cells, particularly in hypoxic tumor environments. A promising approach involves the integration of both PDT and PTT by employing gold-shell isolated nanoparticles (AuSHINs) conjugated with PS molecules, thereby enhancing therapeutic efficacy through a synergistic mechanism. However, several critical aspects require further investigation before clinical application. First, the effectiveness of PTT/PDT could potentially be improved by optimizing nanoparticle targeting strategies, such as functionalizing nanoparticles with tumor-specific antibodies or modifying their delivery method (incubation vs. direct injection). Additionally, it is unclear whether PDT remains an effective therapeutic option in hypoxic tumor conditions. Therefore, this project aims to address these pressing questions through a multidisciplinary approach, leveraging advanced imaging techniques and nanotechnology to optimize nanoparticle-based phototherapies. By integrating expertise from UNESP and Lund University, we seek to advance the development of nanostructured phototherapeutic agents, improve their cellular targeting mechanisms, and assess their efficacy in oxygen-deprived tumor environments. Our findings will contribute to refining PDT/PTT strategies, facilitating their translation into clinical applications, and strengthening international collaboration in cancer research. (AU)