Multifunctional nanostructures applied in the diagnosis of cancer patients and in vitro treatment through the synergy between photothermal and photodynamic therapies

• Grant number: 25/00376-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2025
• End date: February 28, 2029
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Sabrina Aléssio Camacho
• Grantee: Giovanna Eller Silva Sousa
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated research grant: 23/17867-9 - Multifunctional approach of gold nanostructures coated with silica: combining the diagnosis of circulating cancer cells with the tumor phototherapy, AP.JP

Abstract

Leukemia is characterized by the uncontrolled proliferation of abnormal white blood cells in the blood and bone marrow, resulting in 487,294 cases and approximately 305,405 deaths in 2022. The general approach to treatment has not significantly changed in the past 30 years, still relying on intensive chemotherapy induction. Although diagnostic procedures, such as the morphological evaluation of bone marrow samples and blood smears, are relatively simple, detection requires an abnormal blast index of at least 20% in the bone marrow. In this context, the diagnosis of circulating cancer cells (CCC) via DNA fragments, micro-RNA, proteins, and exosomes has gained attention as less invasive detection methods. Indeed, detecting CCCs in body fluids, besides avoiding surgeries, offers significant cost and time-saving benefits, making it a useful method for early cancer detection and metastatic monitoring. Alternative treatments, such as photothermal therapy (PTT) and photodynamic therapy (PDT), are promising therapeutic modalities, involving localized temperature increases and the generation of reactive oxygen species (ROS), respectively, capable of promoting protein denaturation and genetic material degradation in cancer cells. Moreover, the synergy between PTT and PDT can enhance the efficiency of cancer therapy. Thus, combining the diagnosis of CCCs in body fluids with synergistic phototherapeutic treatment (PTT + PDT) presents a promising approach to addressing current cancer treatment challenges and represents a unique opportunity for the development of multifunctional nanostructures. Therefore, the aim of this direct doctoral (DD) project is to develop multifunctional nanostructures based on gold nanostars conjugated with photosensitizing molecules and biofunctionalized with specific molecules for leukemia cells to evaluate their efficiency in two main approaches. In the first approach, the nanostructures will be used to diagnose overexpressed proteins in tumor cells in isolated samples and body fluids from patients with acute myeloid leukemia, such as saliva, sweat, and urine. In the second approach, the nanostructures will be applied to in vitro acute myeloid leukemia (HL-60) systems, aiming for a more efficient treatment through the synergy between PTT and PDT, combined with the specificity provided by biofunctionalization.