Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Targeted drug delivery systems aim to improve therapeutic efficacy for cancer treatment.
• Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely used drug carriers.
• Low folic acid (FA) conjugation efficiency limits the targeting ability of FA-PLGA systems.

Purpose of the Study:

• To develop a novel PLGA-based drug delivery system with a high folic acid conjugation ratio for enhanced cancer cell targeting.
• To evaluate the efficacy of 5-fluorouracil (5-FU) loaded nanoparticles in HT-29 cancer cells.

Main Methods:

• Fabrication of PLGA nanoparticles conjugated with folic acid using 1,3-diaminopropane as a crosslinker.
• Encapsulation of 5-fluorouracil (5-FU) into the prepared nanoparticles.
• In vitro cytotoxicity assays (IC50 determination) and fluorescent microscopy to assess cellular uptake.

Main Results:

• Achieved a high folic acid conjugation ratio of 46.7% (mol/mol) using 1,3-diaminopropane.
• 5-FU loaded PLGA-1,3-diaminopropane-folic acid nanoparticles showed significantly lower IC50 (5.69 µg/mL) against HT-29 cells compared to 5-FU alone (22.9 µg/mL) and 5-FU loaded PLGA nanoparticles (14.17 µg/mL).
• Fluorescent microscopy confirmed enhanced uptake of FA-conjugated nanoparticles by HT-29 cancer cells, indicating superior targeting affinity.

Conclusions:

• 1,3-diaminopropane effectively facilitates high-ratio folic acid conjugation to PLGA, creating a novel polymer.
• The developed 5-FU loaded PLGA-1,3-diaminopropane-folic acid nanoparticles represent a highly efficient system for targeted drug delivery to cancer cells.