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Developing a molecularly-correlated AC biosusceptometry system to detect and quantitate nerve fiber damage

Grant number: 17/00842-2
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 22, 2017
Effective date (End): January 21, 2018
Field of knowledge:Biological Sciences - Biophysics - Biophysics of Processes and Systems
Principal researcher:José Ricardo de Arruda Miranda
Grantee:Caio César Quini
Supervisor abroad: Philip John Horner
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Research place: Houston Methodist, United States  
Associated to the scholarship:15/14914-0 - AC Biosusceptometry to assess accumulation of cancer-targeted magnetic nanoparticles in tumors for diagnostic and therapy, BP.PD


The central nervous system (CNS) is composed of neurons and support cells (glial cells). These cells are responsible for several functions, including structural and metabolic support, insulation, and guidance of development. The unique molecular nature of the different types of nerve damage, such as severe demyelination or fiber disruption, as well neural regeneration states, hinder such functions by offsetting the quality of electromagnetic conductivity of the fibers, misbalancing magnetic flux in the microneighborhood of nerves. Nerve fiber damage, regardless its origin, will impair the ability to conduct impulses. The methods currently employed for characterizing such damage, although well described, are extremely time consuming and do not provide in vivo information, which is a crucial barrier towards translational applications. Magnetic nanoparticles, however, offer a simpler and easier alternative to track specific markers with considerable advantages, such as in vivo monitoring and quantitative information ex vivo. We hypothesize that the ACB technique, combined with an MRI system, can be employed to assess nerve fiber damage, differentiating lesion subtypes between severe demyelination, and partial or total fiber disruption based on magnetic biomarkers quantification. In order to enhance specific signal in areas of interest, we will employ magnetic nanoparticles to target biomarkers of degeneration and regeneration in the CNS in combination with MRI and ACB. We will utilize citrate coated, manganese ferrite nanoparticles having different biomarkers linked to the surface. The MRI scanning protocol will also be optimized to enhance detection efficiency. After MNPs administration and MRI scan post injection, we will employ the ACB sensor to scan the lesion site to quantify nanoparticles accumulation in each group. In addition to the ACB measurements and MRIs, the lesion site will be scanned postmortem for specific biomarkers+MNP accumulation and molecular data will be assessed by histology. This project will provide the necessary background to significantly expand the range of applications of the AC Biosusceptometry system. By itself, this protocol development creates a new field of ACB applications, based on using the system as a probe for specific biomarkers. Additionally, the conjugation strategy employed here will enable us to bypass biological barriers and directly assess both brain and nerve fiber damage. Such protocol might be the starting point towards more elaborated nanocarriers, targeting specific regions and tissues of interest with application in early diagnosis of diseases and novel therapeutic protocols. (AU)

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Scientific publications
(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)
QUINI, CAIO C.; PROSPERO, ANDRE G.; KONDILES, BETHANY R.; CHABOUB, LESLEY; HOGAN, MATTHEW K.; BAFFA, OSWALDO; BAKUZIS, ANDRIS F.; HORNER, PHILIP J.; MIRANDA, JOSE R. A. Development of a protocol to assess cell internalization and tissue uptake of magnetic nanoparticles by AC Biosusceptometry. Journal of Magnetism and Magnetic Materials, v. 473, p. 527-533, MAR 1 2019. Web of Science Citations: 1.

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