Abstract
ObjectiveThe 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.Methods and resultsThe 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.ConclusionThe 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.
Highlights
Modern medicine undoubtedly can boast great successes in the control of tumor development and progression
listeriolysin O (LLO) is released into the cell endosome after phagocytosis as its major function is to facilitate L. monocytogenes intracellular survival
LLO exhibits the typical features of the cholesterol-dependent cytolysin with one major exception; it exhibits maximal activity in acidic pH, which is typically observed in the tumor environment [36]
Summary
Modern medicine undoubtedly can boast great successes in the control of tumor development and progression. An increase in cancer-related mortality is still observed in developed countries [1,2,3,4]. This increase is caused by both side effects associated with the conventional treatment (e.g., surgery, radiotherapy and chemotherapy) and low efficiency of used drugs, which are increasingly proven to be inadequate [5]. It is often necessary to use an excess of applied medicines. The benefits obtained from the application of antitumor factors are overshadowed by numerous excessive side effects. Considerable efforts have been made to change this state of affairs and reduce the undesirable effects that are connected with classic anti-tumor therapies
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