Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis

Fei Yu, Jing Li, Ying Xie, Richard L. Sleightholm, David Oupicky

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Chloroquine (CQ) is a widely used antimalarial drug with emerging potential in anticancer therapies due to its apparent inhibitory effects on CXCR4 chemokine receptor, autophagy, and cholesterol metabolism. This study reports on polymeric CQ (pCQ) as a macromolecular drug with antimetastatic activity. The pCQ polymers were synthesized by copolymerization of methacryloylated hydroxy-CQ (HCQ) and N-(2-hydroxypropyl)methacrylamide (HPMA). The results show that pCQ is significantly more effective in inhibiting cancer cell migration and invasion when compared with the parent HCQ. The proposed mechanism of action at least partially relies on the ability of pCQ to inhibit cell migration mediated by the CXCR4/CXCL12 pathway. The pCQ also demonstrates superior inhibitory activity over HCQ when tested in a mouse model of experimental lung metastasis. Lastly, pCQ shows the ability to efficiently translocate to the cytoplasm while exhibiting lower cytotoxicity than HCQ. Overall, this study supports pCQ as a promising polymeric drug platform suitable for use in combination antimetastatic strategies and potential use in cytoplasmic drug delivery.

Original languageEnglish (US)
Pages (from-to)347-356
Number of pages10
JournalJournal of Controlled Release
Volume244
DOIs
StatePublished - Dec 28 2016

Fingerprint

Chloroquine
Cell Movement
Neoplasm Metastasis
Lung
Pharmaceutical Preparations
CXCR4 Receptors
Neoplasms
Chemokine Receptors
Autophagy
Antimalarials
Polymers
Cytoplasm
Theoretical Models
Cholesterol
Therapeutics

Keywords

  • CXCR4
  • Chloroquine
  • Endosomal release
  • HPMA
  • Metastasis
  • Polymeric drug

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis. / Yu, Fei; Li, Jing; Xie, Ying; Sleightholm, Richard L.; Oupicky, David.

In: Journal of Controlled Release, Vol. 244, 28.12.2016, p. 347-356.

Research output: Contribution to journalArticle

Yu, Fei ; Li, Jing ; Xie, Ying ; Sleightholm, Richard L. ; Oupicky, David. / Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis. In: Journal of Controlled Release. 2016 ; Vol. 244. pp. 347-356.
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