Nanomedical approach in targeted therapy of breast cancer: use of carbon nanostructures
Authors:
M. Löffelmann 1; S. Skaličková 2; M. Gargulák 1; M. Dočekalová 1; M. Kepinská 3; B. Ruttkay-Nedecký 1; P. Suchý 2; R. Kizek 1,2,3
Authors place of work:
Veterinární a farmaceutická univerzita Brno
Farmaceutická fakulta
; Centrální laboratoře
Přednosta: prof. Ing. René Kizek, DrSc., MBA
1; Ústav humánní farmakologie a toxikologie
Přednosta: doc. MVDr. Pavel Suchý, Ph. D.
2; Ústav biomedicínských a environmentálních analýz
Wroclaw Medical University, Wroclaw, Polsko
Přednosta: prof. Dr. hab. Halina Milnerowicz, MD
3
Published in the journal:
Prakt. Lék. 2017; 97(6): 264-269
Category:
Of different specialties
Summary
Objective:
Main goal of this project was to develop a nanotransporter based on a targeted delivery using oligonucleotide probe, which is complementary to a mutated BRCA1 gene sequence with the expected effect of a cytostatic without significant toxic effects. The mentioned cytostatic is often used doxorubicin. Despite its therapeutic efficacy, however, it exhibits high cardiotoxicity. Nanotransporters represent the possibility of increasing the therapeutic window.
Methods:
Doxorubicin and oligonucleotide probe were bound to fullerenes. The modification time was 24 hours. The nanotransporter was subsequently characterized by biophysical techniques (SEM, dynamic light scattering, spectral and electrochemical methods.) Using the electrochemical and fluorescence analysis the formation of nanotransporter was confirmed.
Results:
Doxorubicin with a negatively charged surface interacts with positively charged fullerenes by electrostatic interaction and this interaction was confirmed by on the basis of electron microscopy (SEM), electrochemically (change of potential was 35 mV) and by measurement of dynamic light scattering (change of ζ-potential was 22 mV). Oligonucleotide probe, which is complementary to the BRCA mutated gene sequence, was bound to the complex by an amide bond. The drop of the fluorescence signal by 80% indicated binding of the oligonucleotide. To demonstrate the functionality, a magnetic gold nanoparticle, modified by the complementary sequence to the tested nanotransporter, was developed.
Conclusion:
We assume, that the proposed nanotransporter will be used for DNA targeted delivery of the antitumor drug to the cells with BRCA mutated genes. The nanotransporter has these basic characteristics: a) fullerene has a high affinity to the cell and penetrates the cell membrane; b) doxorubicin is released into cytoplasm in tumour cells due to low pH; c) the entire construct is targeted to the BRCA mutated gene sequence; d) the gold nanoparticle enhances the cytotoxic effect.
KEYWORDS:
doxorubicin – malignant breast tumours – fullerenes – magnetic gold nanoparticles – oligonucleotide – nanomedicine
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