Monitoring magnetic nanoparticle cell labelling with ultrasound imaging

• Grant number: 22/14228-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2023
• End date: February 29, 2024
• Field of knowledge: Engineering - Biomedical Engineering - Medical Engineering
• Agreement: Delft University of Technology
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Theo Zeferino Pavan
• Grantee: Theo Zeferino Pavan
• Principal researcher abroad: Martin Daniel Verweij
• Institution abroad: Delft University of Technology (TU Delft), Netherlands
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Antonio Adilton Oliveira Carneiro
• Associated research grant: 21/06728-2 - Photoacoustic and ultrasound imaging for theranostic purposes, AP.JP2

Abstract

Nanomedicine has been significantly involved in cancer research because it opens the possibility of new diagnostic and therapeutic approaches to overcome some drawbacks of conventional treatments. For example, to decrease resistance of tumors to chemo- and radiotherapy and control side effects of anti-cancer drug. Superparamagnetic iron oxide (SPIO) nanoparticles are biocompatible and present unique intrinsic properties, which enables them to be used in a wide range of applications. They may be used as contrast agents in several imaging techniques, agents for cell tracking, carriers for targeted drug delivery, as therapeutic agents, and as biosensors. Ultrasound is an imaging technique widely used for medical diagnosis purposes. To achieve ultrasound-based molecular imaging, nanoparticles are often used as molecular contrast agents since these are small enough to cross biological barriers accumulating within the diseased region. However, ultrasound is not adequate for the direct visualization of nanoparticles, since a single nanoparticle or even a cluster of nanoparticles do not allow appropriate contrast. Different strategies have been proposed to overcome this limitation, e.g. photoacoustic and magnetomotive ultrasound (MMUS) imaging. MMUS is an imaging technique where ultrasound is used to map magnetic nanoparticle distribution within tissues, detecting microvibrations originating from the interaction of nanoparticles with an external time-varying magnetic field. A key challenge in molecular imaging is to enhance the sensitivity to detect nanoparticles delivery and internalization by cells. Recent studies have reported on the feasibility of using photoacoustic and MMUS imaging techniques to sense the endocytosis of nanoparticles into living cells. This was achieved because intracellularly accumulated SPIO-nanoparticles generated a nonlinear MMUS signal amplification, while the photoacoustic signal was not affected by the SPIO-nanoparticles delivery. Therefore, the internalization of nanoparticles into the cells was assessed by analyzing the relationship between the photoacoustic and MMUS responses. One method to enhance site-specific nanoparticles delivery to cells involves the use of low diffusible gas-filled encapsulated microbubbles. Under continuous wave ultrasonic irradiation, microbubbles oscillate causing pressure variation in the surrounding medium. This perturbation enhances nanoparticles uptake by the cells via different routes such as sonoporation, enhanced endocytosis, and opening of cell-cell contacts. (AU)