Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.
Chromobacterium violaceum
(
C. violaceum
) is a Gram-negative, rod-shaped facultatively
anaerobic bacterium implicated with recalcitrant human infections.
Here, we evaluated the anti-QS and antibiofilm activities of ethyl
acetate extracts of
Passiflora edulis
(
P. edulis
) on the likely inactivation
of acyl-homoserine lactone (AHL)-regulated molecules in
C. violaceum
both by in vitro and in silico analyses.
Our investigations showed that the sub-MIC levels were 2, 1, and 0.5
mg/mL, and the concentrations showed a marked reduction in violacein
pigment production by 75.8, 64.6, and 35.2%. AHL quantification showed
72.5, 52.2, and 35.9% inhibitions, inhibitions of EPS production (72.8,
36.5, and 25.9%), and reductions in biofilm formation (90.7, 69.4,
and 51.8%) as compared to a control. Light microscopy and CLSM analysis
revealed dramatic reduction in the treated biofilm group as compared
to the control. GC–MS analysis showed 20 major peaks whose
chemical structures were docked as the CviR ligand. The highest docking
score was observed for hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)
ethyl ester bonds in the active site of CviR with a binding energy
of −8.825 kcal/mol. Together, we found that hexadecanoic acid,
2-hydroxy-1-(hydroxymethyl) ethyl ester remarkably interacted with
CviR to inhibit the QS system. Hence, we concluded that hexadecanoic
acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester of
P.
edulis
could likely be evaluated for treating
C. violaceum
infections.
DNA methylation is critical for gene silencing and is associated with the incidence of many diseases, including cancer. Underlying molecular mechanisms of human diseases and tissue-specific gene expression have been elucidated based on DNA methylation studies. This review highlights the advantages and drawbacks of various methylation screening techniques: blotting, genomic sequencing, bisulfite sequencing, methylation-specific PCR, methylated DNA immunoprecipitation, microarray analysis, matrix-assisted laser desorption ionization time-of-flight mass spectroscopy, nanowire transistor detection procedure, quantum dot-based nanoassay, single-molecule real-time detection, fluorimetric assay, electrochemical detection, and atomic force spectroscopy. The review provides insight for selecting a method or a combination of methods for DNA methylation analysis. Convergence of conventional and contemporary nanotechniques to enumerate methylation at specific CpG sites of oncogene would fill the gap in diagnosis of cancer.
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