McCarroll Joshua A, Sharbeen George, Kavallaris Maria, Phillips Phoebe A
Tumour Biology and Targeting Program, Lowy Cancer Research Centre, Children's Cancer Institute, UNSW Sydney, Sydney, NSW, Australia.
Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW Sydney, Sydney, NSW, Australia.
Methods Mol Biol. 2019;1974:329-353. doi: 10.1007/978-1-4939-9220-1_23.
Pancreatic cancer is a lethal malignancy which is refractory to most chemotherapy drugs. Recent landmark studies have shed new light on the complex genetic heterogeneity of pancreatic cancer and provide an opportunity to utilize "precision-based medicines" to target genes based on the genetic profile of an individual's tumor to increase the efficiency of chemotherapy and decrease tumor growth and metastases. Gene-silencing drugs in the form of short-interfering RNA (siRNA) have the potential to play an important role in precision medicine for pancreatic cancer by silencing the expression of genes including those considered difficult to inhibit (undruggable) using chemical agents. However, before siRNA can reach its clinical potential a delivery vehicle is needed to carry siRNA across the cell membrane and into the cytoplasm of the cell. Herein, we detail the methods required to use star polymer nanoparticles to deliver siRNA to pancreatic tumors in an orthotopic pancreatic cancer mouse model to silence the expression of an "undruggable" gene (βIII-tubulin) that regulates pancreatic cancer growth and chemosensitivity.
胰腺癌是一种致命的恶性肿瘤，对大多数化疗药物都具有耐药性。最近具有里程碑意义的研究为胰腺癌复杂的基因异质性带来了新的认识，并提供了一个机会，即利用“精准药物”根据个体肿瘤的基因图谱靶向基因，以提高化疗效率并减少肿瘤生长和转移。短干扰RNA（siRNA）形式的基因沉默药物有可能通过沉默包括那些被认为难以用化学试剂抑制（不可成药）的基因的表达，在胰腺癌的精准医疗中发挥重要作用。然而，在siRNA发挥其临床潜力之前，需要一种递送载体将siRNA穿过细胞膜并输送到细胞的细胞质中。在此，我们详细介绍了在原位胰腺癌小鼠模型中使用星形聚合物纳米颗粒将siRNA递送至胰腺肿瘤以沉默调节胰腺癌生长和化疗敏感性的“不可成药”基因（βIII-微管蛋白）表达所需的方法。
