Promising Strategy for Treating Colorectal Cancer Using Lactoferrin-Decorated Nanoparticles

Strategic Insights -

Researchers from the School of Pharmacy & Technology Management have identified a promising strategy for treating colorectal cancer using methotrexate-encapsulated solid lipid nanoparticles (MTX-SLNs) and lactoferrin-decorated MTX-loaded nanoparticles (MTX-Lf-SLNs). The study demonstrated that these nanoparticles exhibited improved stability, high drug encapsulation efficiency, and enhanced cytotoxicity, inducing apoptosis and stopping cell cycle progression in HCT116 cells. The nanoparticles also showed extended, pH-sensitive drug release and significant anti-angiogenic effects, reducing immune activation and lowering overall toxicity.

Key Takeaways:

  • The research identified MTX-Lf-SLNs as a promising strategy for treating colorectal cancer, with improved efficacy and reduced side effects compared to MTX-SLNs and free MTX.
  • The optimized nanoparticles displayed a spherical shape (~ 160 nm) with high drug encapsulation efficiency (85.87% for MTX-SLNs and 80.11% for MTX-Lf-SLNs).
  • MTX-Lf-SLNs demonstrated higher cytotoxicity (IC50: 0.51 M) than MTX-SLNs and free MTX, inducing apoptosis and stopping cell cycle progression in HCT116 cells.
  • The nanoparticles exhibited extended, pH-sensitive drug release (70% at pH 5.7) and significant anti-angiogenic effects (~ 70% inhibition in CAM assay).
  • Migration assays validated the capacity of the nanoparticles to obstruct cancer cell invasiveness, suggesting a potential to impede metastasis.
  • The study concluded that utilizing the bioactivity of lactoferrin for precise delivery, MTX-Lf-SLNs offer an attractive approach to enhance anti-colon cancer efficacy while reducing unwanted side effects.

Statistics:

  • The nanoparticles exhibited a docking score of -9.316 for Caspase-6, indicating high affinity.
  • The drug encapsulation efficiency of MTX-SLNs was 85.87%, while MTX-Lf-SLNs exhibited 80.11% efficiency.
  • The cytotoxicity of MTX-Lf-SLNs was IC50: 0.51 M, compared to IC50: 1.01 M for MTX-SLNs and IC50: 1.19 M for free MTX.
  • The immune activation was reduced by 17.6 ± 2.1 pg/mL, 20.2 ± 1.9 pg/mL, and 15.4 ± 3.4 pg/mL for TNF-a, IL-6, and IL-1b, respectively.

Sources:

  • Study of caspase-6 activity in aggressive HCT116 cells using methotrexate-encapsulated lactoferrin-conjugated solid lipid nanoparticles via in silico and in vitro approaches. Scientific Reports, 2025;15(1):20775.
  • School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-Be University, Shirpur, Maharashtra, 425405, India.
  • Nature Portfolio, Heidelberger Platz 3, Berlin, 14197, Germany.