Neuro-oncological precision nanomedicines

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According to the world health organisation, the incidence of brain tumours has been rising steadily (up to forty percent) since the late 1970s. World-wide deaths in 2012 were recorded as 189,382 and are predicted to rise by a further twenty-five percent by 2020. Brain tumours are the most common solid tumour in children and the second most common cancer after leukaemia representing twenty-five percent of all primary paediatric tumours, the leading cause of cancer death. Despite the advances in imaging and multi- modality therapy with neurosurgery, radiotherapy and conventional cytotoxic chemotherapy, outcomes for high-risk brain tumours have improved little in the last two decades. When treatments are effective, they are associated with both acute and long-term significant treatment-related side effects. One of the chief obstacles hindering effective therapy for brain tumours is that the brain is very much isolated from the rest of the body with well-gated barriers controlling the trafficking of molecules and macromolecules in and out. In particular, the interface between the circulatory system and the brain tissues, (the blood-brain barrier (BBB) is the largest barrier by surface area, and allows short distance between blood and neural tissue. On top of this, one of the most critical limitations for cancer therapy is our inability to direct anticancer drugs to cancerous cells maximising killing and minimising side effects (often worse than the disease itself). This is due to the fact that cancer cells are the same healthy cells gone wrong and hence share many similarities with the good cells complicating detection and targeting.We propose here the design of ultra-small carriers (as small as a virus and 100 times smaller than cancer cells) that will be equipped with unique chemical signature to target almost exclusively the BBB, cross it, and target brain cancer cells. These nanocarriers will also be able to carry different drugs and deliver them right inside the cells where the drug is most effective.