Gallic acid-coated silver nanoparticles as perspective drug nanocarriers: bioanalytical study

Abstract

The ability of silver nanoparticles (AgNPs) to be used as drug nanocarriers has helped rapidly to invent novel strategies to treat diseases, such as cancer. The nanoparticles may offer a valuable tool to novel pH-sensitive drug delivery systems in the present scenario because of their undergoing mechanisms associated with the regulated dissolution, aggregation, and generation of oxygen radicals as well. These processes could be monitored by electrochemical (bio)sensors that are less money and time-consuming compared to other analytical approaches, however, with comparable analytical performance. In this paper, synthesized and microscopically characterized gallic acid-coated AgNPs (GA-AgNPs) are investigated using spectral and electrochemical methods. To investigate the Ag⁺ release, a 21-day ageing experiment is performed spectrophotometrically, finding that the peak maximum of GA-AgNPs spectra diminished by 24.5%. The highest Ag⁺ content was electrochemically determined in the supernatant solution after centrifugation (6.97 μmol·L^-1), while no significant concentration of silver ions in solution after redispersion was observed (1.26 μmol·L^-1). The interaction experiment indicates a stabilization of GA-AgNPs in the presence of long-chain dsDNA as well as a mutual electrostatic interaction with DNA sugar-phosphate backbone. This interaction mechanism is confirmed by FTIR analysis, showing a shift (1049 to 1061 cm^-1 and 913 to 964 cm^-1) specific to DNA phosphate bands. Finally, doxorubicin-loaded GA-AgNPs are monitored for the specific drug release in the physiological and more reactive weakly acidic microenvironment. Hereby, electrochemical (bio)sensing of GA-AgNPs undergoing mechanisms shows a huge potential to be used for monitoring of drug delivery systems at cancer therapy.

Keywords: Aggregation; DNA interaction; Drug delivery system; Electrochemical biosensor; Silver ion release; Silver nanoparticles.

Fig. 1

Characterization of GA-AgNPs: (a) schematic illustration of AgNPs characteristics and their application in drug delivery system, (b) size distribution diagram, (c) SEM image, and (d) plasmonic signal at 410 nm

Fig. 2

Spectral and visual analysis of GA-AgNPs aggregation: (a) ageing tests showing the aggregation of 16.9 µg mL⁻¹ AgNPs using UV–Vis spectral analysis (up) and visual color changes (down), (b) dsDNA-regulated aggregation of 16.9 µg mL⁻¹ AgNPs in NaCl-free (H₂O) and a phosphate-enriched medium in the absence and presence of various additions of dsDNA using visual (up) and UV–Vis spectral (down) analysis

Fig. 3

Determination of silver ions release: (a) DPAS voltammograms for various concentrations of silver ions in silver nitrate solution, (b) a corresponding calibration curve, and (c) DPAS voltammograms for original GA-AgNPs and dispersed after centrifugation

Fig. 4

Electrochemical analysis of the GA-AgNPs-dsDNA interaction using a dsDNA/GCE biosensor: (a) cyclic voltammograms and (b) Nyquist plots of 1 mmol L⁻¹ [Fe(CN)₆]^3−/4− as well as (c) DP voltammograms of guanine (+ 0.90 V) and adenine (+ 1.15 V) residues of dsDNA before and after the exposure of the dsDNA/GCE biosensor to the 16.9 µg mL⁻¹ AgNPs colloid for given periods

Fig. 5

Spectral analysis of GA-AgNPs and their interaction with dsDNA: FTIR spectra of dsDNA in the absence (red) and presence (black) of GA-AgNPs showing the electrostatic interaction with the DNA phosphate backbone

Fig. 6

Drug-loaded GA-AgNPs in physiological and acidic microenvironment: (a) UV–Vis absorption spectra of 20.0 µg·mL⁻¹ NBD-Cl (340 nm) and its ROS-induced oxidation product (470 nm) in the presence of 16.9 µg·mL⁻¹ AgNPs colloid in the UV-A irradiation for given periods, (b) evaluation of regulated ROS formation upon DOX loading on GA-AgNPs surface tested in physiological and weakly acidic medium