A novel dual-carrier ultrasmall nanomedicine for the treatment of stroma-rich pancreatic cancer

摘要 胰腺癌（PC）在全球范围内的年发病率超过495，000例， 年死亡率近46万例。大多数患者确诊较晚， 接受切除手术，因此依靠药物治疗来延长生命。电流 治疗仅提供有限的益处， 保护肿瘤。Duo Oncology正在开发一种超小纳米颗粒， 吉西他滨和免疫调节趋化因子受体2型拮抗剂杀死癌症 细胞和增强抗肿瘤免疫力。这些小纳米颗粒，小于30纳米， 直径，显示增强的外渗和组织渗透，特别是在PC肿瘤中 富含致密基质。此外，本文提出的研究将为未来的DUO-307做好准备。 IND使能性研究，包括使用 尖端离体肿瘤外植体模型和PC的临床相关小鼠模型， 致密基质。

Abstract Pancreatic cancer (PC) has an annual worldwide incidence of more than 495,000 cases and an annual mortality rate of almost 460,000 cases. Most patients are diagnosed late and cannot undergo resection and therefore rely on pharmacotherapy to extend their lives. Current therapies offer only limited benefit due in large part to the dense stroma tissue that surrounds and protects the tumor. Duo Oncology is developing an ultra-small nanoparticle containing, gemcitabine and an immunomodulatory chemokine receptor type 2 antagonist to kill cancer cells and invigorate anti-tumor immunity. These small nanoparticles, less than 30nm in diameter, show enhanced extravasation and tissue penetration, particularly in the PC tumors enriched with dense stroma. Further, research proposed herein will prepare DUO-307 for future IND-enabling studies with formulation optimization, toxicology, and therapeutic efficacy using a cutting edge ex vivo tumor explant model and a clinically-relevant mouse model of PC with dense stroma.