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Uptake Dynamics of Cubosome Nanocarriers at Bacterial Surfaces and the Routes for Cargo Internalization.

Brendan P DyettHaitao YuSampa SarkarJamie B StrachanCalum John DrummondCharlotte E Conn
Published in: ACS applied materials & interfaces (2021)
Antibiotic-resistant bacteria pose a significant threat to humanity. Gram-negative strains have demonstrated resistance to last resort antibiotics, partially due to their outer membrane, which hinders transport of antimicrobials into the bacterium. Nanocarrier (NC)-mediated drug delivery is one proposed strategy for combating this emerging issue. Here, the uptake of self-assembled lipid nanocarriers of cubic symmetry (cubosomes) into bacteria revealed fundamental differences in the uptake mechanism between Gram-positive and Gram-negative bacteria. For Gram-positive bacteria, the NCs adhere to the outer peptidoglycan layers and slowly internalize to the bacterium. For Gram-negative bacteria, the NCs interact in two stages, fusion with the outer lipid membrane and then diffusion through the inner wall. The self-assembled nature of the cubosomes imparts a unique ability to transfer payloads via membrane fusion. Remarkably, the fusion uptake mechanism allowed rapid NC internalization by the Gram-negative bacteria, overcoming the outer membrane responsible for their heightened resilience. Here this is demonstrated by the marked reduction in the minimal inhibition concentration required for antibiotics against a pathogenic strain of Gram-negative bacteria, Escherichia coli. These results provide mechanistic insight for the development of lipid NCs as a new tool to combat bacteria.
Keyphrases
  • gram negative
  • drug delivery
  • multidrug resistant
  • escherichia coli
  • cancer therapy
  • drug release
  • fatty acid
  • single cell
  • depressive symptoms
  • pseudomonas aeruginosa