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crIpeC nAnomedicines’ micRodistribution in tUmour tiSsue

Periodic Reporting for period 1 - ICARUS (crIpeC nAnomedicines’ micRodistribution in tUmour tiSsue)

Período documentado: 2020-10-01 hasta 2021-11-30

Nanomedicines (NM) are considered a key instrument to achieve personalized and targeted medicine, aiming to improve therapies and lives of patients suffering from a variety of serious and complex disorders, including cancer, cardiovascular diseases, multiple sclerosis, diabetes as well as different kinds of serious infectious or inflammatory diseases (e.g. arthritis). The advancement of the nanomedicine field has been hindered by the lack of comprehensive understanding of the NM’s (1) macrodistribution in systemic circulation, evidenced by their limited improvements in pharmacokinetics (PK) and tumour uptake, and (2) microdistribution profile once it has reached the complex tumour microenvironment (TME) and exact drug exposure levels to its molecular target. Cristal Therapeutics focuses on the creation of the next generation of (targeted) NM, annd has developed CriPec: a nanoparticle technology that can entrap a wide range of drugs, transforming them into custom-made NM.

ICARUS aims to obtain the critical insights into CriPec’s intratumoral behaviour that will lead CT to optimise the composition and, thus, biological performance of CriPec-based products. This will be achieved by integrating the (bio)analytical chemistry expertise in highly advanced mass spectrometry missing in CT, and conducting state-of-the-art research that, until now, has been out of reach from the NM field. The intention for ICARUS is to uncover the microdistribution of CriPec® in tumour tissue via so-called Mass Spectrometry Imaging as developed and available by M4I (University Maastricht). The major tasks to accomplish this goal include WP 2.1 Detection of CriPec® and API in tumor tissue, WP 2.2 Microlocalization at the cellular level of the CriPec®-API composition in tumour tissue, and WP 2.3 Spatiotemporal insight in CriPec®-API microlocalization and API release kinetics in tumor tissue. Alongside working in the translational science and being trained in the nanotechnology field, the industrial associate will obtain business expertise, getting acquainted with aspects of business development and IP throughout her employment by Cristal Therapeutics.

In the ICARUS project, significant fundamental and translational research progress was made. To accomplish the various tasks, instrumentation was evaluated for the detection of nanomedicine in biological conditions prior to a mouse model. The insight gained from the experiment led to identification of instrument signals which are representative of the nanomedicine material. This method was used on the mouse model samples to detect the circulating nanomedicine in the tumour microenvironment. The current method enables to detect nanomedicine in biological matrices, and consequently to follow the biological faith (incl. spatiotemporal monitoring) of various new CriPec drug products, thus facilitate their development.

The MSI method development and particularly the identification of the nanoparticles in actual mouse tumour samples are truly innovative findings as MSI measurements of CriPec® had never been attempted by Cristal Therapeutics nor by M4i. The current method enables to follow the biological faith (incl. spatiotemporal monitoring) of various new, label-free CriPec drug products. These two institutions benefited greatly from the development of this project and there is already explicit interest from both companies as well as academia to continue the exploration of the in vivo microlocalization of nanomedicines.

Besides, the industrial associate has been fully introduced into the process of drug development within a SME incl. all business facets as well as graduated the EY training package.
The aim of ICARUS was to uncover the microdistribution of CriPec® drug in tumour tissue via Mass Spectrometry Imaging (MSI). After extensive optimisation of both matrix and equipment, a best matrix for drug and CriPec® ionization was identified (namely 1,5-diaminonaphthalene (1,5-DAN)) in combination with state-of-the-art MSI equipment (so-called solariX FTICR-MS).

Hereafter, tissue spiked samples were analysed and CriPec® could be detected also in biological matrices.

The MSI method development and particularly the identification of the nanoparticles in actual mouse tumour samples are truly innovative findings as MSI measurements of CriPec® had never been attempted. The current method enables to detect CriPec in biological matrices, and consequently create opportunity to follow the biological faith (incl. spatiotemporal monitoring) of various new CriPec drug products.

Besides, the industrial associate has been fully introduced into the process of drug development within a SME incl. all business facets as well as graduated the EY training package.
The MSI method development and particularly the identification of the nanoparticles in actual mouse tumour samples are truly innovative findings as MSI measurements of CriPec® had never been attempted by Cristal Therapeutics nor by M4i. The current method enables to follow the biological faith (incl. spatiotemporal monitoring) of various new, label-free CriPec drug products. These two institutions benefited greatly from the development of this project and there is already explicit interest from both companies as well as academia to continue the exploration of the in vivo microlocalization of nanomedicines.

Besides, the industrial associate has been fully introduced into the process of drug development within a SME incl. all business facets as well as graduated the EY training package, which will boost the rest of her career.
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