Optimization of photodynamic therapy through the combination with sonodynamic therapy for the treatment of basal cell carcinoma

• Grant number: 25/11565-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Physics - General Physics
• Principal Investigator: Vanderlei Salvador Bagnato
• Grantee: Erika Toneth Ponce Ayala
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07276-1 - CEPOF - Optics and Photonic Research Center, AP.CEPID

Abstract

Photodynamic therapy (PDT) is a non-invasive therapeutic modality used to combat non-melanoma skin cancer and other precancerous lesions. PDT involves three essential components: a photosensitizer (PS), light at an appropriate wavelength to excite the PS, and oxygen molecules present in the tissue. The interaction of these three elements can generate reactive oxygen species (ROS), leading to cell death in the target tissue. Several clinical studies have reported excellent cosmetic results, absence of side effects, and high cure rates in basal cell carcinoma (BCC) lesions. However, the attenuation of light through tissues is a disadvantage that limits the success of PDT to superficial skin lesions with less than 2.0 mm of infiltration. Sonophotodynamic therapy (SPDT) is a non-invasive anticancer approach based on the combination of PDT and sonodynamic therapy (SDT). SDT is an anticancer technique that involves the combined use of low-intensity ultrasound and a sonosensitizing drug (SS) in the presence of molecular oxygen. Unlike light, ultrasound is a mechanical wave with excellent penetration into biological tissues, allowing the induction of cytotoxic effects in deeper layers of the target tissue. In this context, considering ultrasound's ability to easily travel through many centimeters of tissues, SDT aims to improve PDT cure rates in cases where the low penetration of light through biological tissues and the pigmentation of lesions limit the success of the treatment. There is a well-established protocol called PDT single-visit , in which two PDT sessions are performed on the same day, using 3 hours of incubation of the precursor cream (methyl aminolevulinate, MAL) before the first session, and 1.5 hours of incubation before the second session. This protocol presents response rates of 80.4%, 74.1%, and 50% after 30 days for the treatment of superficial (sBCC), nodular (nBCC), and pigmented (pBCC) basal cell carcinoma lesions, respectively. This project aims to develop a randomized, controlled clinical trial to evaluate the efficacy and safety of a new protocol called Sono-PDT single-visit. The protocol is intended to treat thick and/or pigmented lesions, such as nBCC and pBCC, maintaining the conditions of the conventional single-visit PDT protocol, with the addition of a single dose of low-intensity therapeutic ultrasound (225 J/cm²) after each light session, with the goal of enhancing the therapeutic response. In parallel with clinical study, in vitro studies will be conducted to clarify various uncertainties still present in the literature regarding the mechanisms of action involved in sonodynamic therapy. (AU)