Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells.

Lei Qi,Ruiying Yan,Tongwei Zhang,Shuli Li,Yuhua Xue,Xiujuan Lv,Liming Dai,Ruitao Zou,Peina Jia

doi:10.1038/srep26961

Abstract

A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

Highlights

Injection of chemically synthesized magnetic nanoparticles (MNPs) in mice[12], Xenopus and zebrafish[12,13] does not damage retinal structure
The UV absorption of the extracted supernatants at 260 and 280 nm decreased at each step until they reached zero (Fig. S1a), and no proteins were detected at the fifth step by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Fig. S1b), indicating that the Bacterial magnetosomes (BMs) were free from other cellular protein fractions
The surfaces and cores of the BMs and MNPs were further characterized by Fourier transform infrared spectroscopy (FTIR), zeta potential, magnetic hysteresis curves and high-resolution transmission electron microscopy (HRTEM)

Summary

Introduction

Injection of chemically synthesized MNPs in mice[12], Xenopus and zebrafish[12,13] does not damage retinal structure. The biocompatibility of BMs must be assessed prior to use in ophthalmology applications, but studies of the biocompatibility of BMs have been limited. Sun et al.[14] demonstrated that BMs induced little pathological damage in important organs in rats and little cytotoxicity against H22, HL60 and EMT-6 cells. Liu et al.[15] reported that BMs mainly accumulated in the rat spleen and liver and were completely excreted in 42 days. Human ocular exposure to BMs is unavoidable, among patients using BM-based medicines and workers handling these materials and the wastes of BM products, emphasizing the importance of evaluating the ocular biocompatibility of BMs. Here, we perform a detailed study of the biocompatibility of BMs in terms of both intraocular cytotoxicity and genotoxicity. Commercial MNPs with similar morphologies, sizes and surface groups were evaluated as a control

Methods

Results

Conclusion