Understanding the basic mechanisms of ultrasound interaction with sensitizers and biological tissues to improve the sonodynamic therapy.

• Grant number: 23/14868-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics - General Physics
• Principal Investigator: Sebastião Pratavieira
• Grantee: Sebastião Pratavieira
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Cancer treatment techniques based on dynamic reactions, specifically those reliant on producing reactive oxygen species (ROS), are increasingly emerging as efficient, safe options with minimal side effects. The production of ROS within a lesion results in cell death processes, primarily through apoptosis and necrosis. Photodynamic therapy (PDT) is the most widely used technique, generating ROS through the combination of light and a photosensitive molecule. However, other ROS generation methods are also promising in certain situations, such as sonodynamic therapy (SDT), which involves generating ROS through the interaction of low-intensity ultrasound (US) with a sonosensitive agent. SDT offers a non-invasive procedure that can be used to combat cancer cells.Ultrasonic waves have diverse applications in therapies and the diagnosis of human diseases. Among the advantages of US therapies is their ability to easily penetrate biological tissue and their non-absorption by pigmented tumors, making them effective in combating melanoma cells. The propagation of US in tissue can trigger a series of effects capable of causing cellular damage, including acoustic nucleation and cavitation, which is the formation and oscillation of gas and vapor bubbles in the medium.Despite several published in vitro, in vivo, and clinical studies of SDT, there is still no complete understanding of the physical phenomena involved in this technique. Three proposed mechanisms that can result in cell death in TSD are based on the phenomenon of acoustic cavitation. The first mechanism consists of the action of severe mechanical forces (i.e., shock waves, microstreaming, and microjets) on the cell membrane, inducing cell lysis. The second proposed mechanism is based on the phenomenon of sonoluminescence. In this manner, the emission of sonoluminescent light photoactivates the sonosensitizer, following the exact mechanism as PDT, thereby generating ROS. The third mechanism involves the action of microregions of high temperature and pressure generated during inertial cavitation. These extreme conditions result in the pyrolysis of SS and the formation of highly cytotoxic and short-lived ROS. In this project, we aim to establish the physical foundations of SDT by advancing our understanding of acoustic interactions with biological tissues. To achieve this, we will initially model the propagation of US in biological tissues and predict regions of nucleation, and stable and inertial cavitation. With this knowledge, we can quantify and better control the occurrence of each of the proposed mechanisms of SDT action. Subsequently, we will study the interaction of US with different molecules to determine which chemical characteristics result in an efficient sonosensitizer. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PONCE AYALA, ERIKA TONETH; ALVES, FERNANDA; SILVA E CARVALHO, IAGO; SOUZA, MURILO DE OLIVEIRA; BAGNATO, VANDERLEI SALVADOR; PRATAVIEIRA, SEBASTIAO. Assessing reactive oxygen species generation during sonophotodynamic activity using chemical probes. OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXXII, v. 12823, p. 10-pg., 2024-01-01. (13/07276-1, 14/50857-8, 23/14868-4)

ROCHA, MATHEUS B.; PRATAVIEIRA, SEBASTIAO; VIEIRA, RENAN SOUZA; GELLER, JULIANA DUARTE; STEIN, AMANDA LIMA MUTZ; DE OLIVEIRA, FERNANDA SALES SOARES; CANUTO, TANIA R. P.; VIEIRA, LUCIANA DE PAULA; ROSSONI, RENAN; SANTOS, MARIA C. S.; et al. Fluorescence images of skin lesions and automated diagnosis using convolutional neural networks. Photodiagnosis and Photodynamic Therapy, v. 52, p. 15-pg., 2025-04-01. (23/14868-4)

PONCE AYALA, ERIKA TONETH; REQUENA, MICHELLE BARRETO; BAGNATO, VANDERLEI SALVADOR; PRATAVICIRA, SEBASTIAO. Quantification of Protoporphyrin IX in Murine Pigmented Melanoma Induced by Systemic and Topical ALA Administration Protocols. OPTICAL METHODS FOR TUMOR TREATMENT AND DETECTION: MECHANISMS AND TECHNIQUES IN PHOTODYNAMIC THERAPY XXXII, v. 12823, p. 8-pg., 2024-01-01. (13/07276-1, 22/10860-6, 14/50857-8, 23/14868-4)

ANTUNES, CAMILA A.; TOVAR, JOHAN S. D.; PRATAVIEIRA, SEBASTIAO. Theoretical study of the conditions for acoustic nucleation and cavitation in biological tissue for its application in sono-photodynamic therapy. CLINICAL BIOPHOTONICS III, v. 13009, p. 10-pg., 2024-01-01. (13/07276-1, 14/50857-8, 23/14868-4)