Study of the cytotoxicity of low frequency ultrasound associated with Janus-type mesoporous silicon nanoparticles containing nitric oxide.

• Grant number: 24/19379-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2024
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Renata Fonseca Vianna Lopez
• Grantee: Francisco Rinaldi Neto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 22/03521-0 - Investigation of physical methods associated with drug delivery systems in the local immune and antimicrobial response, AP.TEM

Abstract

Sonodynamic therapy (SDT) is a new therapeutic strategy that has been studied for antitumor activity. SDT involves the interaction of ultrasound with a sonosensitizing agent (SS) that, after activation, uses molecular oxygen in the tumor to induce cell death. Although not yet elucidated, the mechanism that causes cell death is attributed to both reactive species produced by SS and the cavitation process induced directly by ultrasound. In this sense, strategies developed to improve the cavitation process may result in increased cytotoxicity. Mesoporous silicon nanoparticles (MSN) have pores of adjustable diameters and volumes, and through selective oxidation methods, Janus-type nanoparticles can be obtained. These nanoparticles contain hydrophobic internal pore walls and a hydrophilic external surface. When dispersed in an aqueous medium, these nanoparticles can trap air in the porous cavities, serving as cavitation nuclei during ultrasound application. However, the study of the behavior of these NSMs under low-frequency ultrasound (LFU) irradiation has never been performed and requires further investigation. Nitric oxide (NO) is a colorless gas involved in several biological processes, including vasodilation, angiogenesis, neurotransmission, and macrophage-mediated immunity. In cancer, high concentrations of NO have antitumor effects, inducing apoptosis and sensitizing tumors to chemotherapy and radiotherapy. The association of NO and NSMs for sonodynamic therapy may not only take advantage of the biochemical effects of NO, but also the physical effects, since this gas can favor nucleation and thus modulate the cavitational process induced by ultrasound. Perfluorocarbon phase change agents are hydrophobic liquids with high gas carrying capacity. They are extensively used as contrast in ultrasound images due to their inert characteristics, and once subjected to ultrasound, they can change phase, forming gases, which enhances the formation of cavitation bubbles. Hydrogels are three-dimensional polymeric networks with high water content, frequently used in biomedical applications. Due to their unique porous structure, high swelling ratio, good mechanical properties, good biocompatibility and the ability to release the therapeutic agent in a temporal pattern, injectable hydrogels have attracted great attention in tumor therapy. Specifically, natural biomaterials based on extracellular matrix (ECM) have become increasingly prevalent in the development of injectable hydrogels. The ECM is composed of structural and functional molecules produced by the intrinsic cells of each tissue and therefore exhibits low inflammatory responses, good biocompatibility and inherent biodegradability. Based on the hypothesis that Janus-type NSMs can efficiently encapsulate NO solubilized in perfluorocarbons and release the gas in a controlled manner by cavitation induced by low-frequency ultrasound, this work proposes the development of these nanoparticles. The biological evaluation will be performed in tumor cell lines, using an injectable hydrogel matrix based on ECM for controlled administration.