Harnessing of Staphylococcus aureus Bacterial Ghosts Loaded with Docetaxel Nanoparticles for Treatment of Breast Cancer

Abstract

Purpose

Bacterial ghosts (BGs) are the bacterial shells of Gram-positive and Gram-negative bacteria devoid of internal contents. This study aimed to utilize S. aureus BGs loaded with pre-prepared nanoparticles (NPs) of DTX as a novel delivery system targeting BC with minimal toxicity. A novel protocol for S. aureus ghost preparation using 7% v/v tween 80 and formic acid was developed.

Methods

The ghosts were characterized by SEM, and protein and DNA release were analyzed spectrophotometrically and via gel electrophoresis. DTX nanoparticles (NPs) were fabricated using antisolvent precipitation, optimized for particle size, zeta potential, and physicochemical properties. The antiproliferative activity of DTX-loaded S. aureus ghosts on breast cancer cells were assessed. In vitro release studies and mathematical release kinetics of DTX from the ghosts were evaluated, along with their cytotoxic activity in MDA-MB-231 cells.

Results

Findings revealed that the S. aureus ghosts were successfully produced by employing our proposed protocol. All tests confirm that the produced ghosts are free of internal and genetic content. The results showed a maximum loading capacity of 37.3 ± 0.8% with a maximum entrapment efficiency of 75.5 ± 0.8%. According to the in vitro release studies conducted on DTX-loaded ghosts over 16 days, there was an initial burst release rate of 53.3% in the first six hours, followed by a sustained release that continued for the entire 16-day period, reaching a maximum release rate of 69.2%. Mathematical analysis of the release kinetics of DTX from S. aureus ghosts indicated that it followed the Higuchi model, suggesting a diffusion process. The application of the Krosmeyer-Peppas model revealed an n value of 0.9473, indicating that the release was non-Fickian or anomalous. The assay of the antiproliferative activity of the prepared loaded S. aureus ghosts by the chemotherapy NPs on the BC cell line was relatively safe with no cytotoxicity. S. aureus BGs loaded with DTX-NPs show sustained release and significant antiproliferative activity against BC cells presenting a promising drug delivery system.

Conclusion

Our study highlights several benefits, such as improved stability and sustained release, which could enhance therapeutic outcomes. The BG-loaded drug approach offers a promising therapeutic strategy for delivering drugs to the targeted tissues for cancer treatment.