Bioengineered bacterial vesicles as biological nano-heaters for optoacoustic imaging

Vipul Gujrati,Michaela Aichler,Jaber Malekzadeh-Najafabadi,Vasilis Ntziachristos,Gabriele Mettenleiter,Axel Walch,Uwe Klemm,Andre Stiel,Jaya Prakash

doi:10.1038/s41467-019-09034-y

Vipul Gujrati, Michaela Aichler + Show 7 more

Open Access

https://doi.org/10.1038/s41467-019-09034-y

Copy DOI

Abstract

Advances in genetic engineering have enabled the use of bacterial outer membrane vesicles (OMVs) to deliver vaccines, drugs and immunotherapy agents, as a strategy to circumvent biocompatibility and large-scale production issues associated with synthetic nanomaterials. We investigate bioengineered OMVs for contrast enhancement in optoacoustic (photoacoustic) imaging. We produce OMVs encapsulating biopolymer-melanin (OMVMel) using a bacterial strain expressing a tyrosinase transgene. Our results show that upon near-infrared light irradiation, OMVMel generates strong optoacoustic signals appropriate for imaging applications. In addition, we show that OMVMel builds up intense heat from the absorbed laser energy and mediates photothermal effects both in vitro and in vivo. Using multispectral optoacoustic tomography, we noninvasively monitor the spatio-temporal, tumour-associated OMVMel distribution in vivo. This work points to the use of bioengineered vesicles as potent alternatives to synthetic particles more commonly employed for optoacoustic imaging, with the potential to enable both image enhancement and photothermal applications.

Highlights

Advances in genetic engineering have enabled the use of bacterial outer membrane vesicles (OMVs) to deliver vaccines, drugs and immunotherapy agents, as a strategy to circumvent biocompatibility and large-scale production issues associated with synthetic nanomaterials
In order to avoid systemic side effects due to bacterial endotoxin lipopolysaccharide (LPS), we use an Escherichia coli strain previously modified to be less endotoxic through inactivation of the msbB gene[16], and we further engineer it to overexpress tyrosinase, which produces melanin that is passively incorporated into the cytosol and membrane of OMVΔmsbB
The idea was that melanin would be produced and would accumulate in the cytosol and periplasmic space, it would be packaged into membrane and cytosol of OMVs that would be shed into the culture medium

Summary

Introduction

Advances in genetic engineering have enabled the use of bacterial outer membrane vesicles (OMVs) to deliver vaccines, drugs and immunotherapy agents, as a strategy to circumvent biocompatibility and large-scale production issues associated with synthetic nanomaterials. OMVs can be customised to carry desired payloads and can be produced in large quantities using fermentation and purification procedures previously optimised on a pilot scale This is beneficial when considering that bacteria can be modified genetically to produce desired agents useful in vaccination, bio-sensing, bioimaging, therapy or targeted delivery; and these agents can be localised in membrane-derived vesicles[16,17,18,19,20]. We hypothesise that we can package naturally occurring melanin into bacterial OMVs to create a biocompatible nanomaterial (OMVMel) for efficiently delivering the photoabsorber to target tissues for optoacoustic imaging and theranostic applications. It may be possible to replace the melanin with other naturally derived theranostic cargos to generate a flexible platform for imaging-based theranostic applications against cancer and other diseases

Methods

Results

Conclusion