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104TE/2022 - Improvement of original antitumor compounds pharmacological parameters using targeted nanoshuttles designed for colorectal cancer modern approach

104TE/2022 – ONCOTARGET
PN – III – P1 – 1.1. – TE – 2021 – 1660

General description

Project Coordinator:  University of Bucharest

Project Director:  Lecturer Ph.D.Bianca Gălățeanu

Contact: bianca.galateanu@bio.unibuc.ro

Funding Agency: UEFISCDI

Project duration: 24 months (13.05.2022 – 12.05.2024)

Total budget: 450.000 RON

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Recent statistics rank colorectal cancer (CRC) as the second cause of cancer-related deaths and third as incidence and highlight the emerging need to improve the currently available therapeutic approaches. In the context of increasing resistance and dose-limiting side effects to traditional chemotherapy, there is a real need for the development of novel therapies, thus improving the current clinical landscape and increasing patients’ survival chances. However, despite identifying novel potent anticancer agents, these exhibit inappropriate pharmacological parameters for subsequent administration. In this context, the present proposal aims to fine-tune the pharmacological profile of novel lanthanide complexes of quinolone derivatives (oxolinic acid, nalidixic acid, and difloxacin) by their entrapment in original HA-poly (DMAEMA) targeted drug-delivery systems approaching colorectal cancer management. More, the current proposal fits within the modern direction of drug repositioning by bringing the activity of ‘older’ drugs back into clinical use for purposes that are outside the scope of the original medical indication.

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Project

Summary
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Project Objectives

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Objective 1

 Compound selection and drug delivery safety assessment

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OBJECTIVE 2

Investigation of human blood/HA-poly (DMAEMA) nanoparticles interaction

OBJECTIVE 3

Evaluation of LCQD drug delivery systems antitumor in vitro efficacy

OBJECTIVE 4

Investigation of LCQD drug delivery systems antitumor potential in vivo

Project Team

Dedication. Expertise. Passion.

Project Phases

Phase I

13.05.2022 - 31.12.2022

Phase II

01.01.2023 - 31.12.2023

Phase III

01.01.2024 - 12.05.2024

Dissemination

Stage I

  • 1 ISI article published: â€‹â€‹Maciuca, A.M., Munteanu, A.C., Mihaila, M., Badea, M., Olar, R., Nitulescu, G.M., Munteanu, C.V. and Uivarosi, V., 2022. A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies. Pharmaceuticals, 15(8), p.1010 - IF: 5.125

  • 1 participation at an international conference: FITC labeled HA-poly (DMAEMA) nanoparticles internalization profile within HT-29 adenocarcinoma cells. Galateanu Bianca, Ginghina Octav, Zamfir Marius, Velonia Kelly, Hudita Ariana. Al 33-lea Congres Mondial IASGO, 28.09.2022 – 01.10.2022, Istanbul, Turcia – poster

  • 3 participation at a national conference:

    • Modeling Colorectal Cancer: From Flat Biology to Next Generation 3D Models. Galateanu Bianca, Ginghina Octav, Zamfir Marius, Mardare Mara, Velonia Kelly, Hudita Ariana. A doua editie a Conferintei OncoHub, 21.09.2022 – 23.09.2022, Brasov, România – oral presentation

    • Effects of Metal Coordination on the Antioxidant and Cytotoxic Properties of the Natural Flavonoid Primuletin. Ticea Alexandra-Cristina, Ungurianu Anca, Margina Denisa, Mihaila Mirela, Hudita Ariana, Galateanu Bianca, Uivarosi Valentina. A doua editie a Conferintei OncoHub, 21.09.2022 – 23.09.2022, Brasov, România – oral presentation

    • In Vitro IC50 Dose Screening for Lanthanide Complexes with Nalidixic Acid for Their Prospective Use in Colorectal Cancer Therapy. Galateanu Bianca, Uivarosi Valentina, Ticea Alexandra-Cristina, Maciuca Ana-Madalina, Ginghina Octav, Mardare Mara, Tanase Bogdan Cosmin, Hudita Ariana. CONFER, 23.11.2022 – 26.11.2022, IaÈ™i, România – poster

Oncohub-2022-Brasov-0044
Oncohub-2022-Brasov-0979
IMG-20220929-WA0007
IMG-20220930-WA0012
IMG-20220929-WA0006
Oncohub-2022-Brasov-0284

Stage II

  • 1 ISI article under evaluation;

  • 4 participation at a international conference:

    • Familial Polyposis – the good, the bad and the ugly. Andrei Vacarasu, Marius Zamfir, Mardare Mara, Irina Bondoc, Dana Cernov, Theodor Comanica-Stinga, Razvan Iosifescu, Ariana Hudita, Bianca Galateanu, Alin Burlacu, Jeanina Valcea, Theodor Voiosu, Andrei Voiosu, Florin Grama, Maria Barbu, Bogdan Tanase, Laurentiu Simion, Octav Ginghina. 42nd Congress of the European Society of Surgical Oncology ESSO, 25 – 27 October 2023, Florence, Italy – poster presentation

    • FITC labeled HA-poly(DMAEMA) nanoparticles internalization profile within HT-29 adenocarcinoma cells. Bianca Galateanu, Octav Ginghina, Kelly Velonia, Ariana Hudita. The 5th Edtition of the International Conference of Material Research and Nanotechnology ICMRN, 20-21 April, 2023, Paris, France – poster presentation

    • Blood - HA - poly(DMAEMA) - nanoparticles interaction assessment for hemocompatibility validation. Ariana Hudita, Octav Ginghina, Kelly Velonia, Bianca Galateanu,. The 5th Edtition of the International Conference of Material Research and Nanotechnology ICMRN, 20-21 April, 2023, Paris, France – poster presentation

    • La(Nal)3 loaded PDMAEMA NPs induce HT-29 adenocarcinoma cells apoptosis in vitro. Bianca Galateanu, Alexandra Cowell, Valentina Uivarosi, Mirto Charitaki, Kelly Velonia, Ariana Hudita, The Anual International Conference of the Romanian Society of Biochemistry and Molecular Biology, 13-15 September 2023, Cluj Napoca, Romania– poster presentation

  • 1 participation at a national conference:

    • Optimization of a flow cytometry protocol for tumor microenvironment characterization. Bianca Galateanu, Ariana Hudita, The 3rd Edition of the OncoHub Conference - Connecting Scientists and Physicians for Next Generation Cancer Management, 20-22 September 2023, Bucharest, Romania–oral presentation

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Stage III

  • 1 ISI article under evaluation;

  • 1 ISI article published: Coanda, M., Limban, C., Draghici, C., Ciobanu, A.M., Grigore, G.A., Popa, M., Stan, M., Larion, C., Avram, S., Mares, C. and Ciornei, M.C., 2024. Current Perspectives on Biological Screening of Newly Synthesised Sulfanilamide Schiff Bases as Promising Antibacterial and Antibiofilm Agents. Pharmaceuticals, 17(4), p.405. (IF = 4.3)

Project main conclusions and impact:

The impact of project 104TE/ONCOTARGET is significant, with the results contributing to the development of an effective strategy to improve the therapeutic efficacy of LCQD compounds, which are poorly soluble in aqueous environments, as well as enhancing their pharmacokinetic parameters, with the prospect of reducing systemic toxicity and increasing therapeutic effectiveness. Moreover, the delivery of LCQD compounds through the developed nanosystems protects blood components from adverse effects associated with the administration of the free compound, as these nanosystems are hemocompatible compared to the unencapsulated La(Nal)â‚‚ compound. In the context of current trends in oncology, which focus on personalized therapies and controlled drug delivery, the use of these nanoparticles for antitumor compound delivery significantly enhances their pro-apoptotic potential and reduces the side effects associated with the administration of LCQD compounds in free form. Thus, the project opens new opportunities for nano-targeted therapies in oncology, with the potential for broad application in other types of cancer, while also supporting the accelerated integration of drug repurposing processes in oncology.

The results obtained within project 104TE/ONCOTARGET highlight the significant potential of using La(Nal)â‚‚-loaded nanoparticles in oncological treatments, particularly for colorectal cancer. These nanosystems provide controlled and targeted release, reducing systemic toxicity and improving antitumor efficacy. Project 104TE/2022 concludes with the validation of an innovative strategy to improve the pharmacological profile of complex combinations of lanthanides and quinolone derivatives (oxolinic acid, nalidixic acid, difloxacin), based on drug-delivery systems developed for the selective and efficient delivery of antitumor compounds, which can significantly diminish the adverse effects associated with traditional administration, such as hemolysis or liver toxicity, while offering patients a safer and more effective therapy.

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