Stabilized nanosystem of nanocarriers with an immobilized biological factor for anti-tumor therapy.
OBJECTIVE
The inadequate efficiency of existing therapeutic anti-cancer regiments and the increase in the multidrug resistance of cancer cells underscore the need to investigate novel anticancer strategies. The induction of apoptosis in tumors by cytotoxic agents produced by pathogenic microorganisms is an example of such an approach. Nevertheless, even the most effective drug should be delivered directly to targeted sites to reduce any negative impact on other cells. Accordingly, the stabilized nanosystem (SNS) for active agent delivery to cancer cells was designed for further application in local anti-tumor therapy. A product of genetically modified Escherichia coli, listeriolysin O (LLO), was immobilized within the polyelectrolyte membrane (poly(ethylenimine)|hyaluronic acid) shells of 'LLO nanocarriers' coupled with the stabilizing element of natural origin.


RESULTS
The impact of LLO was evaluated in human leukemia cell lines in vitro. Correspondingly, the influence of the SNS and its elements was assessed in vitro. The viability of targeted cells was evaluated by flow cytometry. Visualization of the system structure was performed using confocal microscopy. The membrane shell applied to the nanocarriers was analyzed using atomic force microscopy and Fourier transform infrared spectroscopy techniques. Furthermore, the presence of a polyelectrolyte layer on the nanocarrier surface and/or in the cell was confirmed by flow cytometry. Finally, the structural integrity of the SNS and the corresponding release of the fluorescent solute listeriolysin were investigated.


CONCLUSIONS
The construction of a stabilized system offers LLO release with a lethal impact on model eukaryotic cells. The applied platform design may be recommended for local anti-tumor treatment purposes.
Nałęcz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland.
Angelika
A
Kwiatkowska
Nałęcz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland.
Ludomira H
http://orcid.org/0000-0001-7890-0883
LH
Granicka
Nałęcz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland.
Anna
A
Grzeczkowicz
Department of Applied Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Radosław
R
Stachowiak
Department of Applied Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Michał
M
Kamiński
Department of Applied Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Zuzanna
Z
Grubek
Department of Applied Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Jacek
J
Bielecki
Laboratory of Electrochemistry, Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
Marcin
M
Strawski
Laboratory of Electrochemistry, Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
Marek
M
Szklarczyk
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001685:Biological Factors / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D008024:Ligands; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013057:Spectrum Analysis
D000970:Antineoplastic Agents; D001685:Biological Factors; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008024:Ligands