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Folate-functionalized nanoparticles for controlled 5-Fluorouracil delivery.

Yan Zhang1, Jiashi Li, Meidong Lang

  • 1Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Folate receptor overexpression in tumor cells presents a target for cancer therapy.
  • Developing targeted drug delivery systems can improve therapeutic efficacy and reduce side effects.
  • Polymeric nanoparticles offer a versatile platform for encapsulating and delivering chemotherapeutic agents.

Purpose of the Study:

  • To synthesize and characterize folate-conjugated poly(ε-caprolactone-co-4-maleate-ε-caprolactone) nanoparticles loaded with 5-Fluorouracil (5-FU).
  • To evaluate the in vitro drug release kinetics and targeting potential of the developed nanoparticles.
  • To assess the in vitro tumor inhibition efficacy of the folate-targeted nanoparticles compared to non-targeted and free drug formulations.

Main Methods:

  • Carbodiimide coupling reaction for folate conjugation to poly(ε-caprolactone-co-4-maleate-ε-caprolactone) (P(CL-co-MCL)).
  • Solvent-evaporation method for 5-FU loading into P(CL-co-MCL)-folate nanoparticles.
  • Dynamic light scattering (DLS) and scanning electron microscopy (SEM) for nanoparticle characterization.
  • In vitro drug release studies and cell inhibition assays on folate receptor-overexpressing tumor cells.

Main Results:

  • Well-defined spherical nanoparticles with uniform size distribution were successfully prepared.
  • Controlled in vitro release of 5-FU was achieved, with a release half-life of 16.86 hours (26.4 times longer than free 5-FU).
  • 5-FU loaded P(CL-co-MCL)-folate nanoparticles demonstrated enhanced cell inhibition due to targeted delivery to folate receptor-overexpressing tumor cells.
  • Significantly higher tumor inhibition was observed with folate-targeted nanoparticles compared to non-targeted nanoparticles and free 5-FU.

Conclusions:

  • Folate-conjugated P(CL-co-MCL) nanoparticles represent a promising targeted drug delivery system for 5-FU.
  • The enhanced cellular uptake and improved tumor inhibition highlight the potential of this nanocarrier in cancer therapy.
  • These findings suggest broad applicability in biomedical and pharmaceutical fields for improved cancer treatment strategies.