RESUMEN
BACKGROUND: Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot-ß-cyclodextrin-folic acid (QD-ß-CD-FA) platform for targeted and selected delivery of C-2028 unsymmetrical bisacridine in cancer therapy. METHODS: Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD-ß-CD(C-2028)-FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells. RESULTS: C-2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C-2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C-2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen-ß-CD-FA themselves did not induce any toxic responses in studied cells. CONCLUSIONS: In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier (QDgreen-ß-CD-FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.
Asunto(s)
Apoptosis , Portadores de Fármacos , Ácido Fólico , Neoplasias Pulmonares , Neoplasias de la Próstata , Puntos Cuánticos , beta-Ciclodextrinas , Humanos , Masculino , beta-Ciclodextrinas/química , Ácido Fólico/química , Ácido Fólico/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Puntos Cuánticos/química , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Movimiento Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Acridinas/farmacología , Acridinas/administración & dosificación , Acridinas/química , Línea Celular Tumoral , Sistemas de Liberación de MedicamentosRESUMEN
Several medicinally important compounds that bind to dsDNA strands via intercalation (C-1311, C-1305, EtBr), major groove binding (Hoechst 33258) and covalent binding (cis-Pt) were examined. The obtained results suggest that both the transfer of conformation B to C and the denaturation process, for the ligand-dsDNA complexes, except for covalently bound cis-Pt, took place at higher temperatures compared to the unbound helix. Furthermore, much lower currents of electrooxidation of guanine at 100 °C, compared to the currents obtained at this temperature for dsDNA in the absence of ligands, suggest that the binding of ligands affects the way the dsDNA denaturates at increased temperatures and leads to formation of different forms of DNA single strands. The voltammetric results were compared with the data of two spectroscopic techniques: UV-Vis and CD.
Asunto(s)
Acridinas/química , Aminoacridinas/química , Bisbenzimidazol/química , ADN/química , Compuestos Organometálicos/química , Temperatura , Triazoles/química , Animales , Sitios de Unión , Bovinos , Electroquímica , Ligandos , Estructura Molecular , Desnaturalización de Ácido NucleicoRESUMEN
The electrooxidation of short synthetic 20-nucleotides DNA sequences with various amount of guanine molecules has been studied in a wide temperature range by square wave voltammetry and the results were compared with UV-vis and CD spectra. A twofold increase of dsDNA voltammetric peak, related to an increase in the number of electrons transferred in the guanine electrooxidation process was found to begin at a temperature lower by circa 20 °C compared to the well known increase of the dsDNA absorbance upon denaturation. Since the dsDNA voltammetric peaks are related directly to the electrooxidation of guanine and adenine, early conformational changes in dsDNA are responsible for this effect. An increase in percentage of guanine in the DNA chains caused a delay in the conformational, predenaturation changes. An exception to this behavior was found for polyguanine (100% guanine). Interestingly, two distinct ranges of change in ellipticity in the CD spectra correlate well with the changes obtained by voltammetry. We have also checked the influence of OH radicals and UV irradiation on the dsDNA oxidation.
Asunto(s)
Guanina/química , Radical Hidroxilo/química , Oligonucleótidos/química , Rayos Ultravioleta , Dicroismo Circular , Técnicas Electroquímicas , Oligonucleótidos/síntesis química , Oxidación-Reducción , Espectrofotometría Ultravioleta , TemperaturaAsunto(s)
Electroquímica , Oro/química , Peróxido de Hidrógeno/química , Hierro/química , Electrodos , Oxidación-Reducción , Oxígeno/químicaRESUMEN
The electrooxidation of double stranded DNA has been studied in a wide temperature range by cyclic and square wave voltammetries and the results were compared with UV-Vis and CD spectroscopies. A twofold increase of dsDNA voltammetric peaks related to the conformation changes preceding the denaturation process was found to begin at a temperature lower than the well known increase of dsDNA absorbance upon denaturation (the melting point) by circa 20 degrees C. Since the dsDNA voltammetric peaks are related directly to the electrooxidation of guanine and adenine, early conformational changes in guanine-cytosine (G-C) and adenine-thymine (A-T) pairs in dsDNA are possible reasons for the increase of the voltammetric peaks. The above observations prove that the voltammetric methods are much more sensitive to the changes in guanine and adenine base-pairs conformations and indicate increased exposition of guanine and adenine in the reversible stages that precede the denaturation process of dsDNA. Interestingly, two distinct ranges of change in ellipticity in CD spectra correlate well to the changes obtained by voltammetry and UV spectroscopy, respectively. We also checked the influence of an intercalator on the dsDNA denaturation (temperature) plots. The spectroscopic measurements indicated an increase in the stability of the structure of the double stranded helix upon the addition of the intercalator, while voltammetry showed also that the exposition of guanine and adenine for the electrooxidation drops substantially in the region preceding the denaturation process.
Asunto(s)
ADN/química , Temperatura , Animales , Bovinos , Dicroismo Circular , Electroquímica , Electrodos , Desnaturalización de Ácido Nucleico , Espectrofotometría UltravioletaRESUMEN
The influence of stream orientation versus surface of microelectrode detector was examined in the range between vertical and parallel flow for various jet velocities and various levels of supporting electrolyte. The flow cell was equipped with a conical body Pt microdisk electrode, and the measurements involved voltammetry and chronoamperometry. Ferrocene, two its charged derivatives (sodium ferrocenylo sulfate and ferrocenylomethyltrimethylamino hexafluorophosphate) and sodium iodide were employed as the substrates in the experiments. The strongest convectional transport and the highest signal of the analytes was obtained for alpha = 60 degrees (alpha is the angle between the electrode surface and the stream direction). The measured current increased by up to 1.85 times versus the traditional setup, and therefore, this new geometry of the detector is analytically advantageous. The value of alpha corresponding to the highest signal tended to decrease to approximately 45 degrees in the absence of supporting electrolyte provided that either flow rate or analyte concentration was above a certain threshold value. The experiments indicated that the interplay of the convectional and migrational components in the analyte transport is different for the charge increase and the charge cancellation processes. These experimental facts were confirmed by digital simulation results.