Mineralized and GSH-responsive hyaluronic acid based nano-carriers for potentiating repressive effects of sulforaphane on breast cancer stem cells-like properties

Carbohydr Polym. 2021 Oct 1:269:118294. doi: 10.1016/j.carbpol.2021.118294. Epub 2021 Jun 5.

Abstract

Breast cancer stem cell (BCSC) properties are correlated with the malignancy of tumor cells. Sulforaphane (SFN), a natural isothiocyanate, has anti-cancer effects. However, SFN is an oil-like, hydrophobic and unstable substance. To enhance the inhibitory effect of SFN on BCSC-like properties, the mineralized hyaluronic acid-SS-tetradecyl nano-carriers (M-HA-SS-TA) were prepared. The nano-carriers possessed high SFN entrapment rate (92.36%) and drug-loading efficiency (33.64%). The carriers were responsive to the high reducing and mild acidic tumor micro-environment, leading to rapid SFN releasing from SFN-loaded nano-drug (SFN/M-HA-SS-TA). Through the specific recognition of breast cancer cells bearing CD44+ by HA, M-HA-SS-TA nano-carriers showed excellent tumor-targeting ability. Moreover, compared with free SFN, SFN/M-HA-SS-TA showed much stronger inhibition on the BCSC-like properties (invasiveness, self-renewal and tumor growth) both in vitro and in vivo. Together, these results suggested M-HA-SS-TA nano-carriers were promising platforms for tumor-targeted delivery of SFN, enhancing the therapeutic efficacy against BCSC-like properties by SFN.

Keywords: Breast cancer stem cell; Disulfide bond; Hyaluronic acid; Inhibition; Mineralization; Sulforaphane.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Disulfides / chemical synthesis
  • Disulfides / chemistry*
  • Disulfides / metabolism
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Liberation
  • Female
  • Glutathione / metabolism
  • Humans
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / metabolism
  • Hydrogen-Ion Concentration
  • Isothiocyanates / chemistry
  • Isothiocyanates / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • Sulfoxides / chemistry
  • Sulfoxides / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Disulfides
  • Drug Carriers
  • Isothiocyanates
  • Sulfoxides
  • Hyaluronic Acid
  • sulforaphane
  • Glutathione