Fabrication of targeted and pH responsive lysozyme-hyaluronan nanoparticles for 5-fluorouracil and curcumin co-delivery in colorectal cancer therapy

Int J Biol Macromol. 2024 Jan;254(Pt 2):127836. doi: 10.1016/j.ijbiomac.2023.127836. Epub 2023 Nov 4.

Abstract

Green nanotechnology is considered a promising method to construct functional materials with significant anticancer activity, while overcoming the shortcomings of traditional synthesis process complexity and high organic solvents consumption. Thus, in this study, we report for the first time the rational design and green synthesis of functionalized 5-fluorouracil and curcumin co-loaded lysozyme-hyaluronan composite colloidal nanoparticles (5-Fu/Cur@LHNPs) for better targeted colorectal cancer therapy with minimized side effects. The functionalized 5-Fu/Cur@LHNPs exhibit stabilized particle size (126.1 nm) with excellent homogeneity (PDI = 0.1), favorable colloidal stabilities, and excellent re-dispersibility. In vitro cell experiments illustrate that the cellular uptake of 5-Fu/Cur@LHNPs was significantly improved and further promoted a higher apoptosis ratio of HCT-116 cells. Compared with the control group, the 5-Fu/Cur@LHNPs formulation group achieved effective inhibition (60.1 %) of colorectal tumor growth. The alcohol-free self-assembly method to construct 5-Fu/Cur@LHNPs is simple and safe for a translational chemotherapy drug, also to promote more robust delivery systems for treating colorectal cancer.

Keywords: Colorectal cancer; Composite colloidal nanoparticles; Hyaluronan; Lysozyme; Self-assembly.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Curcumin*
  • Drug Carriers / therapeutic use
  • Drug Delivery Systems / methods
  • Fluorouracil
  • Humans
  • Hyaluronic Acid / therapeutic use
  • Hydrogen-Ion Concentration
  • Muramidase
  • Nanoparticles*
  • Particle Size

Substances

  • Fluorouracil
  • Curcumin
  • Hyaluronic Acid
  • Drug Carriers
  • Muramidase
  • Antineoplastic Agents