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Targeted nanoparticles deliver 5-fluorouracil (5-FU) effectively for prostate cancer. This novel approach enhances drug potency and reduces tumor markers in preclinical models.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Prostate cancer is a leading global cancer in men, necessitating advanced chemotherapeutics.
  • Current treatments face challenges in efficacy and targeted delivery.
  • Folate receptor-mediated drug delivery offers a promising strategy for targeting cancer cells.

Purpose of the Study:

  • To develop and optimize 5-fluorouracil (5-FU)-loaded poly-(lactic-co-glycolic acid)-polyethylene glycol-folic acid (PLGA-PEG-FOL) nanoparticles.
  • To evaluate the targeted delivery and therapeutic efficacy of these nanoparticles in prostate cancer models.

Main Methods:

  • Synthesis of PLGA-PEG-FOL conjugate via carbodiimide coupling.
  • Formulation and optimization of nanoparticles using emulsification-solvent evaporation and Box-Behnken design.
  • Characterization of nanoparticle properties (size, PDI, zeta potential, entrapment efficiency).
  • In vitro cytotoxicity assays on PC-3 cells and in vivo studies in a rat model of prostate cancer.

Main Results:

  • Optimized nanoparticles exhibited favorable characteristics: 178.47 nm size, 0.119 PDI, -23.4 mV zeta potential, 78.93% entrapment efficiency, and sustained 5-FU release for 72 h.
  • In vitro studies showed a 1.6-fold decrease in IC50 for 5-FU-loaded nanoparticles compared to free 5-FU.
  • In vivo studies demonstrated significant reduction in prostate index, PSA, and testosterone levels, with histopathological evidence of lesion attenuation.

Conclusions:

  • PLGA-PEG-FOL nanoparticles represent a viable platform for targeted 5-FU delivery in prostate cancer.
  • This targeted approach enhances chemotherapeutic potency and reduces key disease biomarkers.
  • The developed nanoparticles show significant promise for improving prostate cancer treatment outcomes.