BrainMap

Mr. Ionel Fizesan

Ph.D.

Lecturer - UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Researcher | Teaching staff

Curriculum Vitae (23/06/2023)

Expertise & keywords

Dendronized nanoparticles designed for targeted multimodal image guided therapy Call name: P 3 - SP 3.2 - Proiecte ERA.NET
ERANET-EURONANOMED-THERAGET 2020 - 2023

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO); Institut de physique et de chimie des Matériaux de Strasbourg (FR); Université de Mons (BE); Bioemission Technology Solutions Ike (GR); CheMatech macrocycle design solution (FR)

Affiliation:

Project website: https://crissiac.wixsite.com/theraget

Abstract:

The project aims at validating the innovative design of targeting multimodal imaging (MRI, SPECT &PET) and therapeutic (magnetic hyperthermia (MH)) multifunctional nanoplatforms (NPFs) using already validated targeting ligands (TLs) for tumors. NPFs, that will be developed, will allow multimodal imaging and therapy, monitoring the effect of treatment by imaging.

The project consortium proposes i) the engineering of two types of dendronized nanoparticles (DNPs) (one for diagnosis and one combining diagnosis and therapy); ii) the functionalization of DNPs with TLs and/or SPECT/PET probes and iii) preclinical proof-of-concept for improved diagnostics and/or therapy of solid tumors. As a member of the consortium, the Romanian partner is involved in experiments related to the in vitro and in vivo cytotoxicity assays, MH in vitro, and in vivo efficacy of NPFs. The cytotoxicity of NPFs will be studied in vitro, on breast cancer (MCF-7 and MDA-MB-231) and ovarian cancer (SKOV3 and SW626) cell lines, as well as in vivo. The cells will be analyzed to check the expression of apoptotic signature and the plasma membrane integrity. The intrinsic and comparative cytotoxic properties of NPFs will be assessed by using 3 standardized tests: the membrane integrity test by measuring the release of lactate dehydrogenase (LDH) while the metabolic activity by the Alamar blue test and Neutral Red test aiming at establishing the concentration threshold of NPFs corresponding to their intrinsic toxicity. The efficiency of the MH treatment on normal/cancer cells loaded with different amounts of NPFs will be evaluated and the optimal MH parameters (frequency and magnetic field amplitude and the number of MH cycles) will also be determined. The goal is to demonstrate the capability of DNPs to induce in vitro apoptosis of the cancer cells at concentrations below their intrinsic toxicity and in AC magnetic fields satisfying the condition Hxf

Magnetic hyperthermia induced drug release from thermosensitive magneto-liposomes for cancer cells apoptosis Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-1392 2021 - 2022

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://crissiac.wixsite.com/pn-iii-te20-iacovita

Abstract:

The combination of magnetic hyperthermia with chemotherapy through one single versatile nano-platform represents a really promising technology in the treatment of cancer. In this project we propose to further extend the very recent advancements in both preparation and application of thermosensitive magneto-liposomes (ThMLs) to cancer treatment with the precise goal of elaborating a new class of biofunctionalized hybrid ThMLs capable to be easily directed to the tumor site by magnetic field gradients, where an alternating magnetic field can remotely trigger the release of drug increasing thus the drug concentration at the tumor site and decreasing the toxic side effects. Moreover these hybrid ThMLs have a huge potential for synergistically increasing the antitumor activity of the chemotherapy by sensitizing the tumor cells through magnetic hyperthermia. Robust and stealth ThMLs having the transition temperature in between 42-43°C will be prepared. Cubic superparamagnetic iron oxide magnetic nanoparticles (SPIONs) with high heating power will be synthesized and further introduced in the inner cavity of the liposomes together with anticancer therapeutic drugs to complete the preparation of drug-loaded ThMLs. The high thermal energy delivered by encapsulated cubic SPIONs upon exposure to external AC magnetic field within the safety limit, besides altering the liposomal membrane and render it permeable to encapsulated anticancer drug, will also sensitize the cancer cells to chemotherapy. Their intrinsic toxicity and will be assessed by means of 4 complementary types of viability assays on different types of cancer cells. The internalization mechanism of ThMLs into cells and their intracellular distribution as a function of incubation time will be evaluated as well. In the final phase of the project, we will perform in vitro tests on different types of cancer cells incubated with drug-loaded ThMLs in order to prove their sensing, triggering and killing capabilities.

In vitro application of ferrite nanoparticles as novel magnetic hyperthermia agents Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2019-0804 2020 - 2022

Role in this project: Project coordinator

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://ionelfizesan.wixsite.com/pd-ferromagnet

Abstract:

In the present project, we propose to synthesize iron oxide magnetic nanoparticles (IOMNPs) with increased magnetic performance and applicability in the magnetic hyperthermia (MH). In this regard, the IOMNPs will be doped with Co2+, Zn2+, and Mn2+ and further biofunctionalized with PEG. The synthesized nanoparticles will be characterized, and the working conditions will be selected to obtain monodispersed and monocrystalline ferrite MNPs with controlled size and superior magnetic properties. High interest will be manifested towards the recommendations for the standardization of the in vitro testing of nanomaterials. Prior to the cellular-based experimentation, a quantitative (the dose reaching the cellular layer) and qualitative characterization of the MNPs in cellular media will be performed. The biocompatibility of the ferrite MNPs will be evaluated on 3 different cell lines using 4 complementary viability assays. The possible interference of the ferrite MNPs with the biochemical constituents of the assays will be evaluated to avoid false positive/negative results. The mechanisms of toxicity, including generation of oxidative stress, inflammation and cellular death via apoptosis and necrosis will be evaluated for the synthesized MNPs. The ferrite MNPs, with the highest biocompatibility and the heat generation capacity in an alternative magnetic field (AMF), will be evaluated for the MH application. Cancerous and normal cells, exposed to non-toxic doses of MNPs for 24 h, will be further exposed to AMF to induce cellular death. A correlation between the ferrite MNPs composition and physical properties, the heat generation capabilities, and the cellular internalized dose of MNPs with the occurring cellular death will be performed. The parameters used in the MH application will be modified to induce cellular death by apoptosis at temperatures not exceeding 45-46°C. The induction of the apoptosis, as the preferred mechanism of action, will be further evaluated.

Efficient heating agents based on iron oxide magnetic nanoparticles for cancer cells apoptosis by magnetic hyperthermia Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-3283 2020 - 2022

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://crissiac.wixsite.com/pn-iii-ped-iacovita

Abstract:

Magnetic Hyperthermia represents a complementary approach to cancer treatment and it is nowadays in the research spotlight. Its successful application in clinical practice demands biocompatible magnetic nanoparticles with highly improved magnetocaloric properties, able to provide controlled intratumoral heat exposure and to induce cancer cell apoptosis, at safety limit of the magnetic fields for humans. Based on our previous results, related to the synthesis and to the full characterization of polyhedral iron oxide MNPs (IOMNPs), with excellent crystalline, magnetic and hyperthermia properties, we propose to ourselves in this project to demonstrate the ability of our IOMNPs to induce cancer cell apoptosis in vitro at safety limits of the magnetic fields. In this regard, we intend to increase the current biocompatibility and heating performance of polyhedral IOMNPs by coating them with a chemically stable and highly biocompatible silica shell. This will reduce the interparticle dipole-dipole interactions, assuring the stabilization of IOMNPs especially in cellular media and leading to a significant improvement in their heating ability. Moreover, the highly biocompatible characteristic of silica coating will allow exposing the cancer cells to a higher dose of IOMNPs increasing thus their potential to overload the cells. Their intrinsic toxicity and the concentration level below which they are toxic will be assessed by means of four complementary types of viability assays on different types of cancer cells. Finally, hyperthermia experiments will be performed in vitro aiming to demonstrate the capability of silica-coated IOMNPs to effectively induce cancer cells apoptosis below the safety limit of the magnetic fields and at concentration levels below their intrinsic toxicity. Following this strategy we will assure the fulfillment of the objectives of the three R’s principle (replacement, reduction, refinement of animal experiments) before going into animal models.

Advanced Magnetic Nanoparticles with High Heating Power for Cancer Therapy: Synthesis, Biofunctionalization, Cytotoxic and Hiperthermic Properties. Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-0967 2018 - 2020

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Affiliation: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO)

Project website: https://crissiac.wixsite.com/pn-iii-te-iacovita

Abstract:

The Magnetic Hyperthermia (MH) represents a complementary approach to cancer treatment and it is nowadays in the research spotlight. The successful application of MH in clinical practice demands magnetic nanoparticles (MNPs) with highly improved magneto-caloric properties, able to provide controlled intratumoral heat exposure, at safety levels of the magnetic fields, being biocompatible in order to easily circulate through the blood stream, as well. In this project we would like to develop a new class of MNPs with considerably improved magneto-caloric properties by further extending the polyol based synthesis method at elevated temperatures. We propose to increase the synthesis temperature by using polyethyleneglycol (PEG) of higher molecular mass exhibiting higher boiling points or by performing MNPs’ synthesis at higher pressures, thus increasing the boiling point of the solvent. We strongly believe that this approach will enable to highly improve the degree of order of the crystalline structure and to reduce the lattice distortion suffered at the MNPs’ surface, important features governing the magnetic properties and hence the hyperthermia performance of the MNPs. The biocompatibility of the MNPs will be provided through biofunctionalization with PEG, a polymer known to produce “stealth” nanoparticles, by means of different strategies: directly through synthesis or post-synthesis. Their intrinsic toxicity and the concentration level bellow which they are toxic will be assessed by means of 4 complementary types of viability assays on different types of cancer cells (MCF-7, A549, T47D, MDA-kb2). The internalization mechanism of MNPs into cells, their degree of agglomeration and their intracellular distribution as a function of incubation time will be evaluated through Transmission Electron Microscopy as well. Once internalized in the cells the capabilities of the MNPs to hyperthermically induce apoptosis in cell cultures will be tested in vitro.

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects