Page 27
Notes:
Volume 2
Journal of Medical Biotechnology
Biotechnology 2018
July 16-17, 2018
World Biotechnology Congress
July 16-17, 2018 Berlin, Germany
Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of
MamC protein of
Magnetococcus marinus
MC-1
Ana Peigneux
1
, Francesca Oltolina
2
, Irene Masante
2
, Donato Colangelo
2
, Guillermo R Iglesias
1
, Angel V Delgado-Mora
1
, Maria Prat
2
and Concepcion Jimenez-Lopez
1
1
Universidad de Granada, Spain
2
Università del Piemonte Orientale, Italy
M
agnetite Nanoparticles (MNPs) find many applications, including biotechnology, as
they can be manipulated by an external magnetic field and functionalized with different
molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped
magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome
production is still challenging, so bio-mimetics, i.e.
in vitro
magnetite synthesis mediated by
magnetosome-associated proteins is being explored. Our group is working with MamC from
Magnetococcus marinus
MC-1 that controls the morphology and size of the crystals, producing
well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic
at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs
were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody
(mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic
Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the
adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and
cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity
of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells,
while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously
in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and
tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent
effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a
targeted local treatment of tumors with a decrease in the deleterious systemic side effects.
Biography
Ana Peigneux has his expertise in Molecular Biology focused on protein purification for biotechnological applications. Currently, she is pursuing PhD at the
University of Granada, Spain. The main goal of her thesis is the study and the purification of magnetosome-associated proteins to synthesize magnetosome-like
nanoparticles with improved magnetic properties. Moreover, she got two grants to do an Internship in Dr. Prat lab (Italy), where she applied these biomimetic
magnetite nanoparticles as carriers for drug delivery.
apn@ugr.esAna Peigneux et al., J Med Biotechnol 2018, Volume 2