Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles

Piotr Rychahou, Younsoo Bae, Derek Reichel, Yekaterina Y. Zaytseva, Eun Y. Lee, Dana Napier, Heidi L. Weiss, Nick Roller, Heather Frohman, Anh Thu Le, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.

Original languageEnglish
Pages (from-to)85-91
Number of pages7
JournalJournal of Controlled Release
Volume275
DOIs
StatePublished - Apr 10 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors

Keywords

  • CRC lung metastasis
  • Colorectal cancer
  • Nanoparticle therapeutics
  • PI3K inhibitors
  • Polymeric nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

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