Zinc-modified nanotransporter of doxorubicine for multi-targeted therapy of prostate cancer cells.

Skalickova, Sylvie; Loffelmann, Martin; Docekalova, Michaela; Uhlirova, Dagmar; Stankova, Martina; Kepinska, Marta; Milnerowicz, Halina; Fernandez, Carlos; Ruttkay-Nedecky, Branislav; Zidkova, Jarmila; Kizek, Rene

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%.

Citation

SKALICKOVA, S., LOFFELMANN, M., DOCEKALOVA, M., UHLIROVA, D., STANKOVA, M., KEPINSKA, M., MILNEROWICZ, H., FERNANDEZ, C., RUTTKAY-NEDECKY, B., ZIDKOVA, J. and KIZEK, R. 2017. Zinc-modified nanotransporter of doxorubicine for multi-targeted therapy of prostate cancer cells. In Proceedings of the 9th Nanomaterials international conference 2017 (NANOCON 2017): research and application, 18-20 October 2017, Brno, Czech Republic. Ostrava: Tanger Ltd [online], pages 531-536. Available from: https://www.confer.cz/nanocon/2017/read/347-zinc-modified-nanotransporter-of-doxorubicine-for-multi-targeted-therapy-of-prostate-cancer-cells.pdf

• Presentation Conference Type: Conference Paper (published)
• Conference Name: 9th Nanomaterials international conference 2017 (NANOCON 2017): research and application
• Start Date: Oct 18, 2017
• End Date: Oct 20, 2017
• Acceptance Date: Oct 1, 2017
• Online Publication Date: Oct 20, 2017
• Publication Date: Mar 8, 2018
• Publicly Available Date: Dec 18, 2020
• Publisher: Tanger Ltd.
• Peer Reviewed: Peer Reviewed
• Pages: 531-536
• Series ISSN: 2694-930X
• ISBN: 9788087294819
• Keywords: Antracycline antibiotics; Chitosan; Metallothionein; Nano medicine; Nanoparticles; Prostate cancer
• Public URL: https://rgu-repository.worktribe.com/output/247564
• Publisher URL: https://www.confer.cz/nanocon/2017/347-zinc-modified-nanotransporter-of-doxorubicine-for-multi-targeted-therapy-of-prostate-cancer-cells