Abstract
BackgroundGene therapy has gained an increasing interest in its anti-tumor efficiency. However, numerous efforts are required to promote them to clinics. In this study, a novel and efficient delivery platform based on bacterial magnetosomes (BMs) were developed, and the efficiency of BMs in delivering small interfering ribonucleic acid (siRNA) as well as antiproliferative effects in vitro were investigated.ResultsInitially, we optimized the nitrogen/phosphate ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the BMs–PEI–siRNA composites. Furthermore, the prepared nanoconjugates were systematically characterized. The dynamic light scattering measurements indicated that the particle size and the zeta potential of BMs–PEI–siRNA are 196.5 nm and 49.5 ± 3.77 mV, respectively, which are optimum for cell internalization. Moreover, the confocal laser scanning microscope observations showed that these composites were at a proximity to the nucleus and led to an effective silencing effect. BMs–PEI–siRNA composites efficiently inhibited the growth of HeLa cells in a dose-as well as time-dependent manner. Eventually, a dual stain assay using acridine orange/ethidium bromide, revealed that these nanocomposites induced late apoptosis in cancer cells.ConclusionsA novel and efficient gene delivery system based on BMs was successfully produced for cancer therapy, and these innovative carriers will potentially find widespread applications in the pharmaceutical field.
Highlights
Gene therapy has gained an increasing interest in its anti-tumor efficiency
This study reports the synthesis of gene delivery system based on bacterial magnetosomes (BMs) for the effective delivery of small interfering ribonucleic acid (siRNA) by using PEI as a crosslinker (BMs– PEI–siRNA)
The negative surface charge is countered with a positively-charged PEI for the efficient loading of genes, which condenses the anionic siRNA molecules, and interacts with negatively-charged BMs via electrostatic interactions
Summary
We optimized the nitrogen/phosphate ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the BMs–PEI–siRNA composites. The dynamic light scattering measurements indicated that the particle size and the zeta potential of BMs–PEI–siRNA are 196.5 nm and 49.5 ± 3.77 mV, respectively, which are optimum for cell internalization. The confocal laser scanning microscope observations showed that these composites were at a proximity to the nucleus and led to an effective silencing effect. BMs–PEI–siRNA composites efficiently inhibited the growth of HeLa cells in a dose-as well as time-dependent manner. A dual stain assay using acridine orange/ethidium bromide, revealed that these nanocomposites induced late apoptosis in cancer cells
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