Drug Delivery to Keratinocytes and Caco-2 Cells via Ultrasound-Assisted Magnetic Nanoparticles.

• Grant number: 23/11602-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• End date: September 30, 2025
• Field of knowledge: Engineering - Biomedical Engineering - Medical Engineering
• Principal Investigator: Antonio Adilton Oliveira Carneiro
• Grantee: Nícholas Zufelato
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/16939-8 - Development and implementation of novel acoustic, magnetic and optical techniques for diagnostic and therapeutic applications, AP.TEM

Abstract

Numerous conditions can cause the epithelial tissue to sustain injuries, be insufficient, or degenerate, so strategies for repair and regeneration are still being developed. Tissue engineering aims to regenerate organs and tissues, including the skin, by cultivating epithelial cells on biological supports known as scaffolds that can be grafted into patients. Keratinocyte cell culture has demonstrated promising potential for cell grafting in skin repair as an in vitro equivalent model of the epidermis. Furthermore, the combination of magnetic nanoparticles (MNPs) and cell culture has been widely used to gain a better understanding of cellular internalization processes and biocompatibility, as well as to enable cytotoxicity assays and tissue engineering applications. MNPs have attracted considerable interest in a variety of fields, most notably in healthcare. Magnetically mediated control of cellular function has demonstrated potential in tissue engineering. Additionally, topical administration of MNPs offers an intriguing perspective for drug delivery. In this regard, a number of studies utilizing ultrasound based imaging modality as alternative methods for the detection and monitoring of MNPs have emerged in the literature (Almeida et al 2015; Sampaio et al 2017; Hadadian et al 2018; Hadadian et al 2020; and Arsalani et al 2022). The aim of this project is to use magneto-motive ultrasound (MMUS) imaging, a combination of magnetism and ultrasound, to identify the cellular internalization of MNPs in two cell lines, keratinocytes and CaCo2. Furthermore, these MNPs will be encapsulated with organic particles that will aid in the internalization process, allowing us to gain a better understanding of the particle-cell interaction in a keratinocyte and CaCo2 cell culture model. Keratinocytes are epithelial tissue cells with an excellent absorption process, and their use is being investigated in order to internalize MNPs in the cells, allowing external monitoring or a better understanding of biological processes occurring in the epithelial tissue, such as wound healing. There is also interest in developing scaffolds for performing grafts in vivo. The CaCo-2 cell line is a human colon adenocarcinoma cell line that is widely used in drug mechanism research via the gastrointestinal epithelium. As a result, understanding the interaction between MNPs (acting as MMUS markers) and CaCo-2 is essential. The goal of this study is to develop a method for assessing MNP cellular internalization into cells using MMUS. As a result, the current research aims to generate encouraging data that will aid in biological process investigation and preclinical future procedures.