Development of biofunctionalized nanomaterials for biomedical applicationsDevelopment of biofunctionalized nanomaterials for biomedical applications

1.- Design and manufacture of biocompatible and stable nanostructures for RMI contrast agents for in vivo early diagnosis of Alzheimer disease. Alzheimer’s disease (AD) is the leading cause of dementia in the elderly and the most prevalent neurological disease affecting developed countries. The major pathologic hallmarks of AD are extracellular deposits of amyloid peptides in the brain parenchyma that form amyloid plaques (AP) and intracellular accumulation of abnormally phosphorylated tau protein that forms neurofibrillary tangles (NFTs). Currently, the post-mortem histological observation of amyloid plaques and neurofibrillary tangles is the only definitive diagnosis available for AD. Therefore, there is a strong need to develop new techniques to detect these pathologic hallmarks in vivo. This could add a great deal of confidence to the diagnosis of AD and potentially might allow therapeutic intervention much earlier to prevent the rapid progression of the disease. AP are essentially composed of amyloid-beta peptides of 40 or 42 amino acids (Aβ40 or Aβ42). At the present, we are synthesizing new contrast agents for magnetic resonance imaging (MRI) based on functionalized magnetic nanoparticles (MNPs), which specifically recognize amyloid plaques.

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MNPs-BTA-1 nanoconjugate in 5xFAD brain sections. BTA-1 is a fluorescent Thioflavin derivative that exhibits high affinity for amyloid deposits and selectively stains amyloid deposits in the brains of 5XFAD transgenic mice. Micrographs show amyloid plaque accumulation in 5XFAD brain sections stained in green using Thioflavin S (A) and the specific binding of the nanoconjugate MNP-BTA1 to the amyloid plaques (B and C). Fluorescent MNPs are displayed in red (B) and the BTA1 bound to them visualized in blue (C). Scale bar 50mm.

2.- Labeling of human neural precursor cells (hNPCs) with magnetic nanoparticles for in vivo cell tracking in cell replacement therapies against neurodegenerative diseases (i.e. Parkinson disease). One of the goals of stem cell research is the in vitro generation of neurons appropriate for cell replacement therapy in neurodegenerative disorders. These cells could be optimal candidates for developing cell replacement strategies in Parkinson’s disease (PD), a neurodegenerative disorder characterized by a progressive degeneration and loss of nigrostriatal dopaminergic neurons (DAn). In this research line, in collaboration with the Center for Molecular Biology “Severo Ochoa” (CSIC-UAM), we have performed the validation of an efficient protocol to label hNSCs with MNPs. This method to magnetically label hNSCs does not affect cell viability or cell differentiation. Moreover, hNSCs cells labeled with magnetic nanoparticles are detected for long periods of time (up to 5months) by MRI. Functionality of the transplanted cells was analyzed by PET studies.

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Localization of MNPs in 1321N1 cells by confocal laser scanning microscopy. Cells were stained with phalloidin (red), MNPs with an anti-dextran antibody (green) and the nuclei were counterstained with ToPro-3 (blue).

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Longitudinal MRI analysis. MNPs-hNPCs grafted into hemiparkinsonian rat brains can be reliably detected by MR imaging even 5 months after transplantation.

3.-Synthesis of biomaterials from agroalimentary manufacture wastes for bone growth scaffolds. Agricultural wastes are a source of renewable raw materials, with structures that can be tailored for different biomedical applications. They have proved to be good replacement candidates for use as biomaterials for the growth of osteoblasts in bone replacement therapies. In this study, in collaboration with the Institute of Materials Science of Madrid (CSIC) and the Institute of Catalysis and Petroleochemistry (CSIC), several techniques, including X-ray diffraction, chemical analysis, mercury intrusion porosimetry, scanning electron microscopy are used to characterize the biomaterials. Different assays to determine cell viability and osteoblastic differentiation are being used to analyze the biocompatibility of scaffolds produced from beer bagasse, a waste material from beer production.

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In vitro osteoblast growth on Ca-Mg phosphate-cristobalite biomaterials prepared from beer production residues. MC3T3-E1 cells actively adhere to the materials obtained from beer manufacture wastes with no significant changes in cell viability and expressing their typical differentiation markers.

Laboratories:

  • Molecular Biology and Biochemistry: Biofunctionalization
  • Bioinstrumentation and Nanomedicine
  • Bioelectromagnetism
  • Cellular and Animal Models

Productivity

 Contact: Milagros Ramos

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