ZINC-MODIFIED NANOTRANSPORTER OF DOXORUBICINE FOR MULTI-TARGETED THERAPY OF PROSTATE CANCER CELLS

1 SKALICKOVA Sylvie
Co-authors:
1 LOFFELMANN Martin 2 DOCEKALOVA Michaela 2 UHLIROVA Dagmar 2 STANKOVA Martina 3 KEPINSKA Marta 3 MILNEROWICZ Halina 4 FERNANDEZ Carlos 1 RUTTKAY-NEDECKY Branislav 5 ZIDKOVA Jarmila 1,2,3 KIZEK Rene
Institutions:
1 University of Veterinary and Pharmaceutical Sciences Brno, Pharmaceutical Faculty, Brno, Czech Republic, EU
2 Prevention Medicals, Studenka, Czech Republic, EU
3 Wroclaw Medical University, Borowska 211, 50-556, Wroclaw, Poland, EU
4 Robert Gordon University, School of Pharmacy and Life Sciences, Aberdeen, United Kingdom
5 Institute of Chemical Technology, Technicka 3, Prague 166 28, Czech Republic, EU
Conference:
9th International Conference on Nanomaterials - Research & Application, Hotel Voronez I, Brno, Czech Republic, EU, October 18th - 20th 2017
Proceedings:
Proceedings 9th International Conference on Nanomaterials - Research & Application
Pages:
531-536
ISBN:
978-80-87294-81-9
ISSN:
2694-930X
Published:
8th March 2018
Proceedings of the conference were published in Web of Science and Scopus.
Metrics:
18 views / 8 downloads
Abstract

Target therapy for oncologic diseases presents a big challenge for advance nanomedicine. In our work, we focused on multi-target approach development. Designed nanotransporter is based on polysaccharide chitosan which allows formation of nanoparticles. These nanoparticles can bind metal ions, mainly zinc (moreover, zinc stabilizes chitosan structure). The estimated zinc concentration was approximately 1 nmol/g of chitosan. In addition, chitosan nanoparticle (cage) irreversibly binds therapeutics which could be applied for targeted therapy of malignant tumours. Designed chitosan structure (LMQ, 10 g) encapsulation efficiency for doxorubicin was 50%. The pH change (tested interval 5 - 8) caused 20% release of doxorubicin from the nanocage. The nanotransporter is orientated to cancer tissue due the fact that the malignant cells highly express metallothionein (MT). The increased affinity of MT to zinc ions causes that the nanotransporter is preferentially bound to tumour regions with a high MT concentration. Our latest experimental results showed the changes in amino acid metabolism of prostate cancer signalized by increase in the amount of amino acid sarcosine. Therefore, the chitosan-based nanotransporter was modified by anti-sarcosine antibody. The functionality of designed nanotransporter was proved by ELISA with double detection of doxorubicin using fluorescence and by peroxidase activity of ABTS substrate. In another system, magnetic separation and identification of individual components of the nanotransporter were used. The sarcosine binding activity was estimated around 50%.

Keywords: Antracycline antibiotics, chitosan, prostate cancer, metallothionein, nanoparticles, nanomedicine
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