Polymeric Chloroquine as an Effective Antimigration Agent in the Treatment of Pancreatic Cancer

被引:1
作者
Khan, Rubayat [1 ]
Panja, Sudipta [1 ]
Ding, Ling [1 ]
Tang, Siyuan [1 ]
Tang, Weimin [1 ]
Kapoor, Ekta [1 ]
Bennett, Robert G. [2 ,3 ]
Oupicky, David [1 ]
机构
[1] Univ Nebraska Med Ctr, Coll Pharm, Ctr Drug Delivery & Nanomed, Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Univ Nebraska Med Ctr, Dept Internal Med & Biochem & Mol Biol, Omaha, NE 68198 USA
[3] Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68105 USA
关键词
Hydroxychloroquine; pancreatic cancer; metastasis; intraperitoneal administration; polymeric drugs; cancer cell migration; PHASE-I TRIAL; ADVANCED SOLID TUMORS; AUTOPHAGY INHIBITION; INTRAPERITONEAL THERAPY; INDUCED APOPTOSIS; CELL MIGRATION; HYDROXYCHLOROQUINE; DELIVERY; SAFETY; EPIDEMIOLOGY;
D O I
10.1021/acs.molpharmaceut.2c00596
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent.
引用
收藏
页码:4631 / 4643
页数:13
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