Neuro-oncological precision nanomedicines

根据世界卫生组织的数据，自20世纪70年代末以来，脑肿瘤的发病率一直在稳步上升（高达40%）。2012年全球死亡人数为189，382人，预计到2020年将进一步上升25%。脑肿瘤是儿童中最常见的实体肿瘤，也是继白血病之后的第二大常见癌症，占所有原发性儿科肿瘤的25%，是癌症死亡的主要原因。尽管影像学和神经外科、放疗和常规细胞毒性化疗的多模态治疗取得了进展，但在过去二十年中，高危脑肿瘤的结局几乎没有改善。当治疗有效时，它们与急性和长期显著的治疗相关副作用相关。阻碍脑肿瘤有效治疗的主要障碍之一是，大脑与身体的其他部分非常隔离，具有控制分子和大分子进出的门控屏障。特别地，循环系统和脑组织之间的界面（血脑屏障（BBB））是表面积最大的屏障，并且允许血液和神经组织之间的短距离。最重要的是，癌症治疗最关键的限制之一是我们无法将抗癌药物导向癌细胞，从而最大限度地杀死癌细胞并最大限度地减少副作用（通常比疾病本身更糟）。这是因为癌细胞是同样的健康细胞，因此与好的细胞有许多相似之处，使检测和靶向变得复杂。我们在这里提出了超小载体的设计（像病毒一样小，比癌细胞小100倍），它将配备独特的化学特征，几乎只靶向BBB，穿过它，靶向脑癌细胞。这些纳米载体也将能够携带不同的药物，并将它们输送到药物最有效的细胞内。

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.