Conjugated metallothionein-carbon-doxorubicin nanotransporter for targeted breast cancer therapy.

Skali?kov�, Sylvie; Kepinska, Marta; Loffelmann, Martin; Uhl�?ov�, Dagmar; Argul�k, Michael; Do?ekalov�, Michaela; Hosnedlov�, Bo�ena; Ruttkay-Nedeck�, Branislav; Milnerowicz, Halina; Fernandez, Carlos; Kizek, Ren�

Abstract

Metalothionein (MT) is a polypeptide of molecular weight in the range of 6-10 kDa. MT typically contains 60 to 68 amino acid residues. MT is characterized by its unique content of metal ions as well as its sulfur content. Higher MT levels were observed in proliferating cells. This fact demonstrates the importance of MT in the process of cellular regulation (relationship to cancer). The most widely used drug for patients with breast cancer metastases is an anthracycline antitumor antibiotic doxorubicin (DOX). However, the clinical use of DOX is limited by dose-related heart muscle damage (cardiomyopathy), more prevalent with increasing cumulative doses. For this reason, creation of novel pharmaceutical formulations based on using alternative methods as nanocarriers for targeted drug delivery to tumour cells is a crucial task in modern pharmacology. The aim of this work was to design a nanotechnological construct. The construct is designed as two separate nanotransporters. The nanotransporter (A) is formed by an antibody-modified AgNPs particle and a carbon nanotube with encapsulated DOX (AgNPs/Ab1/MWCNT/DOX/ODN1). The nanotransporter (B) is engineered with SPION particle modified with antibody and with bound MT (SPION/Ab2/MT/ODN2). Construct AgNPs/Ab1/MWCNT/DOX/ODN1-SPION/Ab2/MT/ODN2 is formed using an oligonucleotide anchor. Individual parts of the nanotransporter were studied using appropriate methods. The presence of MT was monitored electrochemically by Brdicka method in connection with the transfer technique (AdTSV). Characteristic MT signals RS2CO (-1.15 V), Cat1 (-1.25 V), Cat2 (-1.45 V), Cat3 (-1.75 V) were observed at accumulation time of 120s. SDS PAGE confirmed the presence of MT on SPION nanoparticles at sizes 7 to 15 kDa. The DOX signal was fluorometrically monitored (Em 590 nm, Ex 490 nm). AgNPs sizes ranged from 15-20 nm, and the SPION nanoparticles ranged from 20-50 nm. Additionally, used AgNPs nanoparticles exhibited significant antiproliferative activity (growth inhibition by 20-40%) on a model culture S. Cerevisiae. Created nanoconstruct A showed growth inhibition for S. Cerevisiae by more than 50%. The nanoconstruct after these various analysis shows a high potential as an anticancer drug and may be an innovative way how to deal with the breast cancer in a targeted therapy.

Citation

SKALIČKOVÁ, S., KEPINSKA, M., LOFFELMANN, M., UHLÍŘOVÁ, D., GARGULÁK, M., DOČEKALOVÁ, M., HOSNEDLOVÁ, B., RUTTKAY-NEDECKÝ, B., MILNEROWICZ, H., FERNANDEZ, C. and KIZEK, R. 2018. Conjugated metallothionein-carbon-doxorubicin nanotransporter for targeted breast cancer therapy. In Proceedings of 10th Nanomaterials international conference 2018 (NANOCON 2018): research and application, 17-19 October 2018, Brno, Czech Republic. Ostrava: Tanger Ltd [online], pages 342-347. Available from: https://www.confer.cz/nanocon/2018/download/193-metallothionein-fullerene-doxorubicin-nanotransporter-conjugates-for-targeted-breast-cancer-therapy.pdf

• Conference Name: 10th Nanomaterials international conference 2018 (NANOCON 2018): research and application
• Conference Location: Brno, Czech Republic.
• Start Date: Oct 17, 2018
• End Date: Oct 19, 2018
• Acceptance Date: Sep 30, 2018
• Online Publication Date: Oct 19, 2018
• Publication Date: Feb 28, 2019
• Deposit Date: Aug 8, 2019
• Publicly Available Date: Dec 18, 2020
• Publisher: Tanger Ltd.
• Pages: 342-347
• Series ISSN: 2694-930X
• ISBN: 9788087294895
• Keywords: Anticancer drugs; Biophysical analysis; Carbon nanomaterials; Electrochemical analysis; Nanomedicine
• Public URL: https://rgu-repository.worktribe.com/output/235581
• Publisher URL: https://www.confer.cz/nanocon/2018/193-metallothionein-fullerene-doxorubicin-nanotransporter-conjugates-for-targeted-breast-cancer-therapy