Synergistic interactions between SapC-DOPS and chemotherapy for glioma

描述（由申请人提供）：本提案的长期目标是测试SapC-DOPS的疗效：一种独特的脑肿瘤靶向纳米药物，与化疗联合使用。鞘脂激活蛋白C（SapC）是一种鞘脂激活蛋白，广泛存在于全身，其功能是分解代谢鞘糖脂。SapC在酸性pH下优先与带负电荷的磷脂缔合。当SapC与二油酰磷脂酰丝氨酸（DOPS）偶联时，形成稳定的纳米囊泡，其可以选择性地与癌细胞融合，导致酸性鞘磷脂酶的活化和随后的神经酰胺积累、半胱天冬酶活化和最终的细胞凋亡。在这项提案中，我们试图研究SapC-DOPS和化疗之间的任何协同相互作用，这对神经胶质瘤和其他癌症的未来治疗模式也具有广泛的影响。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to test the efficacy of SapC-DOPS: a unique targeting nanotherapeutic for brain tumors, in combination with chemotherapy. Saposin C (SapC) is a sphingolipid activating protein found ubiquitously throughout the body that functions to catabolize glycosphingolipids. SapC preferentially associates with negatively charged phospholipids at an acidic pH. When SapC is coupled with dioleoylphosphatidylserine (DOPS), stable nanovesicles are formed which can selectively fuse with cancer cells, leading to activation of acid sphingomyelinase and subsequent ceramide accumulation, caspase activation, and eventual apoptosis. In this proposal we seek to investigate any synergistic interactions between SapC-DOPS and chemotherapy, which has broad implications on the future treatment paradigms for glioma and other cancers as well.