Antimicrobial Hybrid Amphiphile via Dynamic Covalent Bonds Enables Bacterial Biofilm Dispersal and Bacteria Eradication

Abstract

To tackle the problems caused by bacterial biofilms, herein, this study reports an antimicrobial hybrid amphiphile (aHA) via dynamic covalent bonds for eradicating staphylococcal biofilms. aHA is synthesized via iminoboronate ester formation between DETA NONOate (nitric oxide donor), 3 4‐dihydroxybenaldehyde, and phenylboronic acid‐modified ciprofloxacin (Cip). aHA can self‐assemble in aqueous solution with an ultra‐small critical aggregation concentration of 3.80 × 10–5 mm and high drug loading content of 73.8%. The iminoboronate ester is sensitive to the acidic and oxidative biofilm microenvironment, liberating nitric oxide and Cip that can synergistically eradicate bacterial biofilms. To this end, aHA assemblies efficiently eradicate staphylococcal infections and ameliorate inflammation in the murine peritoneal and subcutaneous infection models without any notable side effects on normal tissues. Collectively, the aHA assemblies may provide a facile and efficient alternative to the current development of anti‐biofilm therapies.

Lipid Prodrug Nanoassemblies via Dynamic Covalent Boronates

“…The dynamic covalent strategy may provide a successful paradigm for developing prodrug nanoassemblies. Due to the facile reaction procedure and highly selective and reversible nature, the dynamic covalent strategy has been exploited to design stimulus-responsive drug release systems utilizing imine, arylhydrazone, disulfide, boronic ester bonds, or Diels–Alder cycloaddition. , Also, we and others have developed smart systems using the combination of two dynamic covalent bonds, for instance, the iminoboronate bond. − The dynamic covalent strategy has also been employed in fabricating polymeric prodrugs. For example, doxorubicin is often conjugated to the side chains of polymers via hydrazone bonds. − A disulfide bond has been used to conjugate cancer therapeutics such as paclitaxel , and camptothecin (CPT) .…”

pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

“…Biofilms are multicellular aggregates wrapped by extracellular polymers ( Figure a). [ 25,26 ] Since conventional antimicrobials agents do not readily penetrate the biofilm, the concentration of antibiotic required to eradicate the biofilm is 1000 times higher than to kill planktonic bacteria. Since the peptide nanoassemblies exhibited the properties of charge increase and size decrease under the biofilm acidic microenvironment, we hypothesize that peptide nanoassemblies have strong permeability in the biofilm environment (Figure 3b).…”

Dynamic covalent nano-networks comprising antibiotics and polyphenols orchestrate bacterial drug resistance reversal and inflammation alleviation

“…7 c, 7d). This regulation of inflammation cytokines is likely due to the eradication of bacteria at the infection sites [ 24 ]. Indeed, the expression of IL-6 and IL-10 did not show significant differences between the treatment of A1 and A1B1C1 on day 2 post-treatment.…”

“…Usually, these building blocks bond to each other via reversible dynamic covalent bonds, virtually encompassing various possible combinations, and allowing the construction of thermodynamically stable and adaptive processes owing to the dynamic interconversion of the constituents [ [17] , [18] , [19] ]. It has been witnessed that dynamic covalent strategy was applied in fields, such as drug discovery [ 17 , 20 ] and delivery [ 21 ], for applications ranging from cancer therapy to bacterial eradication [ [22] , [23] , [24] ]. In principle, an increase in the valency of the building blocks can lead to more complex topologies and functionalities.…”