Redox responsive xylan-SS-curcumin prodrug nanoparticles for dual drug delivery in cancer therapy

Mater Sci Eng C Mater Biol Appl. 2020 Feb:107:110356. doi: 10.1016/j.msec.2019.110356. Epub 2019 Oct 23.

Abstract

Chemotherapeutic agents with different anticancer mechanisms could enhance therapeutic effect in cancer therapy by their combined application. In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ± 2.52 nm), high drug loading of curcumin (∼ 31.4 wt%) and 5-FUSA (∼ 11.8 wt%) and high stability. The interaction of Xyl-SS-Cur/5-FUSA NPs with blood components was investigated by hemolysis study. The cytotoxicity study demonstrated that Xyl-SS-Cur/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SS-Cur/5-FUSA NPs can serve as a promising drug delivery system in cancer therapy.

Keywords: Cancer therapy; Prodrug; Redox responsive; Self-assembled nanoparticles.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Curcumin / pharmacology
  • Disulfides / chemistry
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Drug Stability
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacokinetics
  • HT29 Cells
  • Hemolysis / drug effects
  • Humans
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy
  • Oxidation-Reduction
  • Particle Size
  • Prodrugs / administration & dosage
  • Prodrugs / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Stearic Acids / chemistry
  • Xylans / chemistry

Substances

  • Disulfides
  • Prodrugs
  • Stearic Acids
  • Xylans
  • stearic acid
  • Curcumin
  • Fluorouracil