Abstract
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.
Original language | English (US) |
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Pages (from-to) | 4631-4643 |
Number of pages | 13 |
Journal | Molecular Pharmaceutics |
Volume | 19 |
Issue number | 12 |
DOIs | |
State | Published - Dec 5 2022 |
Keywords
- Hydroxychloroquine
- cancer cell migration
- intraperitoneal administration
- metastasis
- pancreatic cancer
- polymeric drugs
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery