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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 Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae 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 NS1 and NS2, 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, NS1, and NS2 nanosystems were 67.8, −36.7, and −45.1 mV. Moreover, the particle size distribution of the Au@16-mph-16 gold nanoparticles and NS2 nanoformulation was found to be 2.6 nm and 69.0 nm, respectively. However, for NS1 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 Escherichia coli bacteria was notable, with MIC values of 17 µM for both the NS1 and NS2 nanosystems. The Staphylococcus aureus chart shows a greater inhibition effect of NS2 and NP2 in non-diluted wells, and clearly reveals a great effect on Streptococcus pneumoniae, 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 Streptococcus pneumoniae. 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.

Antimicrobial resistance (AMR) is a serious public health problem worldwide which, according to the World Health Organization (WHO), requires research into new and more effective drugs. In this work, both gold nanoparticles covered with 16-3-16 cationic gemini surfactant (Au@16-3-16) and DNA/tetracycline (DNA/TC) intercalated complexes were prepared to effectively transport tetracycline (TC). Synthesis of the Au@16-3-16 precursor was carried out by using trihydrated gold, adding sodium borohydride as a reducing agent and the gemini surfactant 16-3-16 as stabilizing agent. Circular dichroism and atomic force microscopy techniques were then used to ascertain the optimal R range of the relationship between the concentrations of Au@16-3-16 and the DNA/TC complex (R = CAu@16-3-16/CDNA) that allow the obtainment of stable and compact nanosystems, these characteristics being fundamental for their use as antibiotic transporters. Stability studies over time were carried out for distinct selected Au@16-3-16 and Au@16-3-16/DNA-TC nanoformulations using the ultraviolet–visible spectrophotometry technique, checking their stability for at least one month. In addition, in order to know the charge and size distribution of the nanocomplexes, DLS and zeta potential measurements were performed in the solution. The results showed that the characterized nanosystems were highly charged, stable and of a reduced size (1 μm). Once the different physicochemical characteristics of the gold nanosystems were measured, Au@16-3-16 and Au@16-3-16/DNA-TC were tested on Escherichia coli and Staphylococcus aureus to study their antibacterial properties and internalization capacity in microbes. Differences in the interaction of the precursors and the compacted nanosystems generated were observed in Gram-positive and Gram-negative bacteria, possibly due to membrane damage or electrostatic interaction with internalization by endocytosis. In the internalization experiments, depending on the treatment application time, the greatest bacterial destruction was observed for all nanoformulations explored at 18 h of incubation. Importantly, the results obtained demonstrate that both new nanosystems based on TC and Au@16-3-16 precursors have optimal antimicrobial properties and would be beneficial for use in patients, avoiding possible side effects.