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Advanced hybrid theranostic nanoplatforms for an active drug delivery in the cancer treatment

Periodic Reporting for period 1 - NANO4TARMED (Advanced hybrid theranostic nanoplatforms for an active drug delivery in the cancer treatment)

Periodo di rendicontazione: 2021-01-01 al 2022-03-31

Osteosarcoma is a type of cancer invading in most cases the long bones of the legs but it occurs also in arms. In rare situations, it can develop also in soft tissues surrounding the bones. Teenagers and younger adults are the groups suffering from osteosarcoma the most.

Treatment involves approaches such as chemotherapy, surgical extraction, and radiation therapy. All mentioned methods have their benefits, but also considerably adverse effects with their consequences.

The development of the precisely targeted drug delivery systems based on the new highly potent substances is one of the main research roads with an extremely promising potential to improve the therapy in a groundbreaking way. Drug delivery approach could significantly lower the risk of many side effects and highly increase the efficiency of the treatment at once. This would mean a far-reaching positive impact on several levels – from personal to societal to economic.

The Nano4Tarmed (N4T) project scientifically aims at the development of novel nanomaterial-based drug delivery platforms for the diagnosis and treatment of osteosarcoma. Developed nanoplatforms are based on 2D carbon nanomaterials, including graphene oxide and graphene acid, which are being functionalized by polymers, organo-metallic complexes of platinum, low-molecular selectors, such as hyaluronic acid, and anticancer drugs such as DOX.

Going beyond the research level of the project is the effort of a strong networking plateau to develop a synergistic taskforce, the international scientific cluster fighting with joint expert forces one of the most threating diseases of today´s society. Nano4Tarmed interconnects three research groups across three European countries, namely Palacký University in Czechia, Maynooth University in Ireland and Consiglio Nazionale delle Ricerche in Italy.

The project objectives will lead to establishing a scientific platform with the results further applicable to pharmaceutical practice, including open dialogues with respective companies and dissemination of results through an Open innovation platform.

N4T´s main objectives:

Strengthening
1. knowledge and implementing new approaches to the development of advanced nanocarrier systems for anticancer drug delivery;
2. knowledge of novel platinum-based anti-cancer drugs and study of their effects on cell lines and 3D models;
3. scientific profile and collaborations mainly of early-stage researchers and research management skills of the coordinating institution, establishing new links between the Twinning partners and beyond;
4. the network with the application partners and thus enhancing the competitiveness of the region;
5. and implementing open science models.

The establishment of the scientific cluster will contribute to the world-wide research of nanomaterial-based drug delivery systems for a transport of anticancer drugs such as Pt-based complexes, DOX, actinomycin D and others.
This movement will help to improve the current approaches and to establish the new ones, which will be applicable in the diagnosis and treatment of osteosarcoma and as a consequence, positively impact health of the European and World-wide societies.
The networking part of the N4T project was initiated by the Kickoff meeting (14th January 2021) held due to the Covid-19 pandemic online. 14 people attended: 5 from UP, 3 from ISTEC,3 from MU and 3 from the EC. The meeting covered introduction of the partners, description of the project and its work packages, main objectives and approaches.
The launch of the website (www.nano4tarmed.com) followed in February 2021. A discussion platform was added to the website in December 2021. It´s has been updated regularly.

The process of the long-term stay preparation started by an approval of the selection criteria for ESRs in March 2021. Based on these criteria, the first two candidates, Jan Belza and Ludmila Zarska, were selected (6/2021). Ludmila went for a long-term stay to ISTEC in September 2021, Jan went to NUIM in October 2021. Both ESRs presented their findings and research results during two separate seminars (12/2021 and 1/2022).
Ludmila has started her second long-term stay at ISTEC in April, 2022. Jan´s second visit of NUIM is in the process of preparation.

Next to the long-term stays, the ESRs involved in the project attended an online technology transfer training organized by NUIM (11/2021) with a follow-up part planned for Fall 2022, and a training on building of strategic partnerships (3/2022).
The second vital part of the networking activities of the N4T is the education and training of UP´s research management and administration staff (RMAS). The RMAS attended several training courses and professional events during 2021 and 2022, including Europa Media online training, a series of seminars focused on Research Management provided by NUIM (online) and EARMA (European Association of Research Managers and Administrators) conference in Oslo.
More activities are planned in the second half of 2022, including school on biomaterials and visits at research offices at NUIM and ISTEC.

The research results accomplished by the N4T consortium include publication of 2 scientific papers. Obtained results will also be presented on the TERMIS conference in Krakow (6/2022)).

From the scientific perspective, first, we studied interaction of Pt-based complexes prepared by the team at NUIM with cancer cell lines located in the laboratory at ISTEC. The results have showed a potential of the anticancer activity of the developed compounds on several types of cancer cell lines. The results were published in Frontiers in Chemistry (Moynihan E., et al. Click Pt(IV)-Carbohydrates Pro-Drugs for Treatment of Osteosarcoma, Frontiers in Chemistry, 2021) and orally presented at 5th Symposium of Irish Biological Inorganic Chemistry (26/11/2021).
Next, we developed a novel method for the diagnosis of prostate cancer using nanomaterial-based plasmonic sensors and published the obtained results in Frontiers in Analytical science (Chaloupkova Z., et al., Label-Free Determination of PSA and Free PSA Using MA-SERS, Frontiers in Analytical Science, 2022).

All results will be treated according to the Data management plan, prepared according to the FAIR principles in June 2021.
The research activities performed within the framework of Nano4Tarmed have been focused on the development and studies of interactions of novel nanomaterial-based drug delivery carriers with selected cancer cell lines. We developed a 2D nanosystems based on the graphene oxide, functionalized using biocompatible polymer (PEG) and Pt-based complexes. The toxicity and performance of the nanosystem to deliver the Pt based drugs were evaluated on various cell lines, including gliomas, breast cancer and osteosarcoma. The obtained results have showed high loading capacity of the system and high stability. We will continue the development of the nanoplatforms in a way allowing to bind more drug combinations, including DOX and Actinomycin D and to selectively target the platform towards cancer cell lines using vectors based on hyaluronic acid or similar low-molecular substances, which are selective to CD-44 present dominantly on the surface of cancer cells. Simultaneously, the methods for a monitoring of distribution of the nanoplatforms in the cellular environment, which are based on fluorescence and Raman markers, are being actively developed and tested.
Lida Zarska (UP) at partner laboratory (ISTEC)