Hyaluronic acid-decorated liposomal nanoparticles for targeted delivery of 5-fluorouracil into HT-29 colorectal cancer cells

Behzad Mansoori, Ali Mohammadi, Fereydoon Abedi-Gaballu, Soheil Abbaspour, Mehri Ghasabi, Reza Yekta, Solmaz Shirjang, Gholamreza Dehghan, Michael R. Hamblin, Behzad Baradaran

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

The use of liposomes as drug carriers improves the therapeutic efficacy of anticancer drugs, while at the same time reducing side effects. Hyaluronic acid (HA) is recognized by the CD44 receptor, which is overexpressed in many cancer cells. In this study, we developed HA-modified liposomes encapsulating 5-fluorouracil (5-FU) and tested them against a CD44 expressing colorectal cell line (HT29) and a non-CD44 expressing hepatoma cell line. The average size of 5-FU-lipo and 5-FU-lipo-HA nanoparticles were 112 ± 28 and 144 ± 77 nm, respectively. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay showed selective cancer cell death depending on the CD44 expression in a time-dependent manner. Apoptosis assays and cell-cycle analysis indicated that G0/G1 arrest occurred. The colony formation study revealed that cells treated with 5-FU-lipo and 5-FU-lipo-HA had reduced colony formation. Quantitative reverse-transcription polymerase chain reaction study showed that the oncogenic messenger RNA and microRNA levels were significantly reduced in the 5-FU-lipo-HA-treated group, while tumor suppressors were increased in that group. We suggest that optimal targeted delivery and release of 5-FU into colorectal cancer cells, renders them susceptible to apoptosis, cell-cycle arrest, and decreased colony formation.

Original languageEnglish
Pages (from-to)6817-6830
Number of pages14
JournalJournal of Cellular Physiology
Volume235
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020
Externally publishedYes

Keywords

  • 5-fluorouracil
  • CD44
  • apoptosis
  • cell cycle
  • clonogenicity
  • colorectal cancer
  • hyaluronic acid
  • liposomes
  • microRNA

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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