Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance

Compacted Au@16-mph-16/DNA-AMOX (NSi) nanosystems were prepared from amoxicillin (AMOX) and precursor Au@16-mph-16 gold nanoparticles (Ni) using a Deoxyribonucleic acid (DNA) biopolymer as a glue. The synthesized nanocarrier was tested on different bacterial strains of <i>Escherichia coli</...

Full description

Bibliographic Details
Main Authors: Rosa M. Giráldez-Pérez, Elia M. Grueso, Alfonso Carbonero, Juan Álvarez Márquez, Mirian Gordillo, Edyta Kuliszewska, Rafael Prado-Gotor
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/8/1275
_version_ 1827730661555830784
author Rosa M. Giráldez-Pérez
Elia M. Grueso
Alfonso Carbonero
Juan Álvarez Márquez
Mirian Gordillo
Edyta Kuliszewska
Rafael Prado-Gotor
author_facet Rosa M. Giráldez-Pérez
Elia M. Grueso
Alfonso Carbonero
Juan Álvarez Márquez
Mirian Gordillo
Edyta Kuliszewska
Rafael Prado-Gotor
author_sort Rosa M. Giráldez-Pérez
collection DOAJ
description Compacted Au@16-mph-16/DNA-AMOX (NSi) nanosystems were prepared from amoxicillin (AMOX) and precursor Au@16-mph-16 gold nanoparticles (Ni) using a Deoxyribonucleic acid (DNA) biopolymer as a glue. The synthesized nanocarrier was tested on different bacterial strains of <i>Escherichia coli</i>, <i>Staphylococcus aureus,</i> and <i>Streptococcus pneumoniae</i> to evaluate its effectiveness as an antibiotic as well as its internalization. Synthesis of the nanosystems required previous structural and thermodynamic studies using circular dichroism (CD) and UV-visible techniques to guarantee optimal complex formation and maximal DNA compaction, characteristics which facilitate the correct uptake of the nanocarrier. Two nanocomplexes with different compositions and structures, denoted NS<sub>1</sub> and NS<sub>2</sub>, were prepared, the first involving external Au@16-mph-16 binding and the second partial intercalation. The Ni and NSi nanosystems obtained were characterized via transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) techniques to measure their charge, aggregation state and hydrodynamic size, and to verify their presence inside the bacteria. From these studies, it was concluded that the zeta potential values for gold nanoparticles, NS<sub>1</sub>, and NS<sub>2</sub> nanosystems were 67.8, −36.7, and −45.1 mV. Moreover, the particle size distribution of the Au@16-mph-16 gold nanoparticles and NS<sub>2</sub> nanoformulation was found to be 2.6 nm and 69.0 nm, respectively. However, for NS<sub>1</sub> nanoformulation, a bimodal size distribution of 44 nm (95.5%) and 205 nm (4.5%) was found. Minimal inhibitory concentration (MIC) values were determined for the bacteria studied using a microdilution plates assay. The effect on <i>Escherichia coli</i> bacteria was notable, with MIC values of 17 µM for both the NS<sub>1</sub> and NS<sub>2</sub> nanosystems. The <i>Staphylococcus aureus</i> chart shows a greater inhibition effect of NS<sub>2</sub> and NP<sub>2</sub> in non-diluted wells, and clearly reveals a great effect on <i>Streptococcus pneumoniae</i>, reaching MIC values of 0.53 µM in more diluted wells. These results are in good agreement with TEM internalization studies of bacteria that reveal significant internalization and damage in <i>Streptococcus pneumoniae</i>. In all the treatments carried out, the antibiotic capacity of gold nanosystems as enhancers of amoxicillin was demonstrated, causing both the precursors and the nanosystems to act very quickly, and thus favoring microbial death with a small amount of antibiotic. Therefore, these gold nanosystems may constitute an effective therapy to combat resistance to antibiotics, in addition to avoiding the secondary effects derived from the administration of high doses of antibiotics.
first_indexed 2024-03-11T00:10:52Z
format Article
id doaj.art-b92322bb66ad40639d93f6a9b809e283
institution Directory Open Access Journal
issn 2079-6382
language English
last_indexed 2024-03-11T00:10:52Z
publishDate 2023-08-01
publisher MDPI AG
record_format Article
series Antibiotics
spelling doaj.art-b92322bb66ad40639d93f6a9b809e2832023-11-18T23:59:22ZengMDPI AGAntibiotics2079-63822023-08-01128127510.3390/antibiotics12081275Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic ResistanceRosa M. Giráldez-Pérez0Elia M. Grueso1Alfonso Carbonero2Juan Álvarez Márquez3Mirian Gordillo4Edyta Kuliszewska5Rafael Prado-Gotor6Department of Cell Biology, Physiology and Immunology, Faculty of Sciences, University of Cordoba, 14014 Cordoba, SpainDepartment of Physical Chemistry, Faculty of Chemistry, University of Seville, 41012 Seville, SpainDepartment of Animal Health, Veterinary Faculty, University of Cordoba, 14014 Cordoba, SpainDepartment of Cell Biology, Physiology and Immunology, Faculty of Sciences, University of Cordoba, 14014 Cordoba, SpainDepartment of Animal Health, Veterinary Faculty, University of Cordoba, 14014 Cordoba, SpainChemtra Company, 47-300 Krapkowize, PolandDepartment of Physical Chemistry, Faculty of Chemistry, University of Seville, 41012 Seville, SpainCompacted Au@16-mph-16/DNA-AMOX (NSi) nanosystems were prepared from amoxicillin (AMOX) and precursor Au@16-mph-16 gold nanoparticles (Ni) using a Deoxyribonucleic acid (DNA) biopolymer as a glue. The synthesized nanocarrier was tested on different bacterial strains of <i>Escherichia coli</i>, <i>Staphylococcus aureus,</i> and <i>Streptococcus pneumoniae</i> to evaluate its effectiveness as an antibiotic as well as its internalization. Synthesis of the nanosystems required previous structural and thermodynamic studies using circular dichroism (CD) and UV-visible techniques to guarantee optimal complex formation and maximal DNA compaction, characteristics which facilitate the correct uptake of the nanocarrier. Two nanocomplexes with different compositions and structures, denoted NS<sub>1</sub> and NS<sub>2</sub>, were prepared, the first involving external Au@16-mph-16 binding and the second partial intercalation. The Ni and NSi nanosystems obtained were characterized via transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) techniques to measure their charge, aggregation state and hydrodynamic size, and to verify their presence inside the bacteria. From these studies, it was concluded that the zeta potential values for gold nanoparticles, NS<sub>1</sub>, and NS<sub>2</sub> nanosystems were 67.8, −36.7, and −45.1 mV. Moreover, the particle size distribution of the Au@16-mph-16 gold nanoparticles and NS<sub>2</sub> nanoformulation was found to be 2.6 nm and 69.0 nm, respectively. However, for NS<sub>1</sub> nanoformulation, a bimodal size distribution of 44 nm (95.5%) and 205 nm (4.5%) was found. Minimal inhibitory concentration (MIC) values were determined for the bacteria studied using a microdilution plates assay. The effect on <i>Escherichia coli</i> bacteria was notable, with MIC values of 17 µM for both the NS<sub>1</sub> and NS<sub>2</sub> nanosystems. The <i>Staphylococcus aureus</i> chart shows a greater inhibition effect of NS<sub>2</sub> and NP<sub>2</sub> in non-diluted wells, and clearly reveals a great effect on <i>Streptococcus pneumoniae</i>, reaching MIC values of 0.53 µM in more diluted wells. These results are in good agreement with TEM internalization studies of bacteria that reveal significant internalization and damage in <i>Streptococcus pneumoniae</i>. In all the treatments carried out, the antibiotic capacity of gold nanosystems as enhancers of amoxicillin was demonstrated, causing both the precursors and the nanosystems to act very quickly, and thus favoring microbial death with a small amount of antibiotic. Therefore, these gold nanosystems may constitute an effective therapy to combat resistance to antibiotics, in addition to avoiding the secondary effects derived from the administration of high doses of antibiotics.https://www.mdpi.com/2079-6382/12/8/1275gold nanoparticlesantibiotic resistanceaureus nanosystemgemini surfactantamoxicillin
spellingShingle Rosa M. Giráldez-Pérez
Elia M. Grueso
Alfonso Carbonero
Juan Álvarez Márquez
Mirian Gordillo
Edyta Kuliszewska
Rafael Prado-Gotor
Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
Antibiotics
gold nanoparticles
antibiotic resistance
aureus nanosystem
gemini surfactant
amoxicillin
title Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
title_full Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
title_fullStr Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
title_full_unstemmed Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
title_short Synergistic Antibacterial Effects of Amoxicillin and Gold Nanoparticles: A Therapeutic Option to Combat Antibiotic Resistance
title_sort synergistic antibacterial effects of amoxicillin and gold nanoparticles a therapeutic option to combat antibiotic resistance
topic gold nanoparticles
antibiotic resistance
aureus nanosystem
gemini surfactant
amoxicillin
url https://www.mdpi.com/2079-6382/12/8/1275
work_keys_str_mv AT rosamgiraldezperez synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT eliamgrueso synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT alfonsocarbonero synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT juanalvarezmarquez synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT miriangordillo synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT edytakuliszewska synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance
AT rafaelpradogotor synergisticantibacterialeffectsofamoxicillinandgoldnanoparticlesatherapeuticoptiontocombatantibioticresistance