Title: Nanobugs as drugs: Bacterial derived nanomagnets enhance tumor targeting and oncolytic activity of HSV-1 virus

Abstract

The survival strategies of infectious organisms have inspired many therapeutics over the years. Indeed, the advent of oncolytic viruses (OVs) exploits the uncontrolled replication of cancer cells for production of their progeny resulting in a cancer targeting treatment that leaves healthy cells unharmed. Their success against inaccessible tumours, however, is highly variable due to inadequate tumour targeting following systemic administration. Nanotechnology is paving the way for new carrier systems designed to overcome this challenge. Until recently, a biologically derived alternative to metallic particles, namely bacterial-derived magnetosomes, has been relatively overlooked presumably due to the challenges associated with their biomanufacturer. They possess many advantages including a narrow size and shape distribution and a biologically compatible surface chemistry, which prevents aggregation and provides an anchor for functional groups for biotechnology applications. Here we demonstrated their nanocarrier capabilities by co-assembly with herpes simplex virus-1 for the treatment of mammary carcinoma. This provides a magnetic coat of armour for the virus shielding the virus from immune attack in the blood stream. Magnetosomes thus enabled tumour targeting from the circulation with magnetic guidance and enhanced viral replication within tumours. This approach was associated with a significant increase in the recruitment/activation of cytotoxic T cells and reprograming of the tumour microenvironment towards a pro-inflammatory phenotype resulting in significant tumour shrinkage and increased survival in a syngeneic mouse model of breast cancer by 50%. Exploiting the properties of such a versatile nanocarrier offers an exciting, novel approach for active tumour targeting to disseminated neoplasms.