BrainMap

Mr. Razvan Ghiarasim

PhD student - INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI"

PhD student

My name is Razvan Ghiarasim and I am a PhD student in the field of chemistry, developing a series of inorganic and organic nanoparticles with the property of broad-spectrum drug delivery.

Curriculum Vitae (24/02/2023)

Expertise & keywords

Restore Her2 dependent sensibility using AXL inhibitors packed in pH dependent nanostructures Call name: EEA Grants - Proiecte Colaborative de Cercetare
EEA-RO-NO-2018-0246 2021 - 2024

Role in this project: Key expert

Coordinating institution: INSTITUTUL REGIONAL DE ONCOLOGIE IAŞI

Project partners: INSTITUTUL REGIONAL DE ONCOLOGIE IAŞI (RO); INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO); OSLO UNIVERSITETSSYKEHUS HF (NO)

Affiliation: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Project website: https://www.nanoher2restore.ro/

Abstract:

This project (NANOHER2RESTORE) proposes to apply modular supramolecular assembly consisting of pH sensitive units, recognition moieties and functional molecules to build up therapeutic entities sensitive to the tumour microenvironment and to investigate mechanisms for targeted breast cancer treatment in vitro and in vivo.

Our concept is based on the utilization of the specific extratumoral pH values as trigger for the targeted localized delivery by nano modular assemblies. The pH dependent self-assembly of the modules is ensured by the presence of block copolymers able to self-assemble into bilayers or vesicles. Furthermore, increasing the hydrophilic volume fraction favors the formation of structures with greater interfacial curvature, such as cylindrical or spherical micelles. These nano/micro structures can be used to encapsulate therapeutics (HER2 blockers and AXL inhibitor, doxorubicine, etc.), to protect the therapeutic agent (upon injection into the body) and to improve circulation times, thereby increasing the amount of active drug that reaches the targeted site. Specific coupling will be used for targeting molecules (trastuzumab) in order to protect Her antigen recognition site and use this recognition to enhance distribution in tumor site, based on over expression of Her on cellular membranes. Once the nano carrier reaches its target site, the drug is released by stimulus-triggered changes to the micelle, passive EPR effect on vesicle nanostructure to accomplish its therapeutic goal. We will use the modified acidic microenvironment of the tumor to produce a structural change in the co-polymeric blocks leading to disorganization of micelle type nanostructures, leading to drug deployment of the desired drug. Axl inhibitors are targeting the Her2 pozitive breast cancer cells in an effort to block an escape mechanism after long standing Her blockade.

The advantage of this delivery method is that we target tumor tissue using pH variations in the microenvironment and concentrate in the same area a dual approach of the tumor cells with both Her2 antibodies (trastuzumab) which remains active on the copolymer branch, as well as an AXL inhibitor. Delievered in the same are they aim to reactivate the Her2 blockade efficacy and render breast cancer cells sensitive to trastuzumab.

Modular Approach to the Synthesis of Multifunctional Polymer Coated Nanoparticles for Applications in Nanomedicine Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2019-0922 2020 - 2022

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI"

Project partners: INSTITUTUL DE CHIMIE MACROMOLECULARA "PETRU PONI" (RO)

Affiliation:

Project website: https://sorinibanescu.wixsite.com/modnanompol

Abstract:

Nanomedicine has the potential to enable early detection and prevention and to drastically improve diagnosis, treatment and follow-up of many diseases including cancer but not only. It will provide the right tools for personalized, targeted and regenerative medicine by delivering the next level of new drugs, treatments and implantable devices to clinicians and patients, for real breakthroughs in healthcare. The main objective of the project is to prepare new materials as modular and versatile platforms based on inorganic core coated with multifunctional polymers, belonging to the 4th generation of nanocarriers, with potential application in molecular detection, imaging and drug delivery systems. Various systems could be realized based on the model platform developed within this project using libraries of nanoparticles, ligands and active principles. To prove the efficiency and the practicality of such a system magnetite will be used as core nanoparticle, taking advantage of its response to external factors (magnetic field) and its suitability for imagistic technique. The research will also benefit from the non-fouling proprieties from polymeric materials with PEG side-chains such as poly hydroxyethyl methacrylate (PHEMA) and poly(oligo(ethylene glycol) methacrylate (POEGAMA) and the high density of hydroxyl functional groups offered by the grafting from approach. Folic acid will be used as a ligand towards tumour cells as they present an excess of folate receptor. Two systems will be also generated where folic acid will be coupled to the polymer brush modified nanoparticles via pH sensitive imine bonds or stable amide bonds. All synthesized materials will be fully characterized regarding their physico-chemical properties and biocompatibility. Also their ability to selectively bind to receptor cells will be verified.

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