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

• Published in: Molecular pharmaceutics Vol. 19; no. 12; pp. 4631 - 4643
• Main Authors: Khan, Rubayat, Panja, Sudipta, Ding, Ling, Tang, Siyuan, Tang, Weimin, Kapoor, Ekta, Bennett, Robert G., Oupický, David
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05.12.2022
• Subjects: Antineoplastic Agents - therapeutic use; Chloroquine - pharmacology; Chloroquine - therapeutic use; Humans; Hydroxychloroquine - pharmacology; Hydroxychloroquine - therapeutic use; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Polymers - therapeutic use; cancer cell migration; pancreatic cancer; Hydroxychloroquine; polymeric drugs; metastasis; intraperitoneal administration
• ISSN: 1543-8384; 1543-8392; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.2c00596

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.