Engineering Starch-Based Nanoparticles and Nanoparticle Clusters for Improving Local Drug Delivery to Tumour Cores and the Brain

使用纳米颗粒输送药物已在多个案例中被证明可以提高药物到达目标部位的**能力，特别是在药物必须**进入细胞内才能发挥作用和/或药物必须通过难以穿透的生物屏障**从血液输送**的情况下(例如，进入大脑或通过致密组织，如肿瘤肿块)。由我们的合作伙伴EcoSynthetix开发的淀粉纳米颗粒(SNPs)**在这种情况下具有特别的药物输送潜力，因为它们在制造过程中能够直接装载药物**，它们的尺寸非常小，它们的凝胶性质(因此**有可能在压力下变形)，以及它们的生物惰性。然而，使用SNPs进行药物输送有两个**固有的限制：(1)SNPs的药物释放非常快**由于其多孔结构和(2)SNPs的小尺寸，虽然非常适合穿透**大脑或深入肿瘤，但也导致SNPs从正常循环**相对较快地清除，限制了SNPs将药物运送到靶点的能力。在这项提案中，**我们的目标是通过(1)设计SNPs的表面来调整药物**释放速率到所需的值，以及(2)开发制造具有良好循环性能的SNPs受控簇**的方法，这些SNPs可以在需要药物释放**的地方选择性地降解**(通过目标位置的特定化学或在**特定时间后通过外部激活)。我们预计，这种基于SNP的材料将显著改善药物的输送，不仅在肿瘤深处，而且在脑部和大脑内(我们的两个**概念验证演示)，而且还将改善有效治疗受到药物运输**限制的其他疾病。这种能力预计将改善**加拿大患有此类疾病的人的健康状况，并为**EcoSynthetix提供一个新的增值市场，将促进加拿大创造新的就业机会。

Delivering drugs using nanoparticles has been demonstrated in multiple cases to improve the**ability of drugs to get to their target sites, particularly in cases in which drugs must be**transported inside cells to be functional and/or drug must be transported from the blood**through hard-to-penetrate biological barriers (e.g. into the brain or through dense tissues such**as tumour masses). Starch nanoparticles (SNPs), developed by our partner EcoSynthetix,**have particular potential for drug delivery in this context given their capacity for direct loading**of drug during fabrication, their extremely small sizes, their gel-like properties (and thus**potential to deform under stress), and their biological inertness. However, there are two**inherent limitations to using SNPs for drug delivery: (1) drug release from SNPs is very fast**given their porous structures and (2) the small size of SNPs, while ideal for penetrating into**the brain or deep into tumours, also induces relatively fast clearance of SNPs from normal**circulation, restricting the capacity of SNPs to transport drugs to target sites. In this proposal,**we aim to address these challenges by (1) engineering the surface of SNPs to adjust drug**release rates to desired values and (2) developing methods of fabricating controlled clusters**of SNPs with good circulation properties that can be selectively degraded where drug release**is desired (either by specific chemistry at the target site or by external activation after a**specific time). We anticipate that such SNP-based materials will significantly improve the**delivery of drugs not only deep inside tumours and both into and within the brain (our two**proof-of-concept demonstrations) but also other diseases in which effective therapy is limited**by drug transport. Such capacity is anticipated to both improve health outcomes for**Canadians suffering from such diseases as well as provide a new, value-added market to**EcoSynthetix that will promote new job creation in Canada.