Dual responsive gelatin-based nanoparticles for enhanced 5-fluorouracil efficiency.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Severe diseases require advanced therapeutic delivery methods.
• Stimuli-responsive nanomaterials are crucial for effective drug delivery vehicles.
• Gelatin-based nanoparticles (NPs) show promise for intracellular drug delivery.

Purpose of the Study:

• To develop gelatin-based NPs for targeted delivery of the anticancer drug 5-fluorouracil (5-FU).
• To utilize the RGD motif in gelatin for tumor cell targeting via integrins.
• To enhance intracellular drug release through a charge-reversal mechanism, avoiding lysosomal degradation.

Main Methods:

• Formulation of 5-FU-loaded gelatin-based NPs.
• Leveraging the RGD motif for integrin-mediated tumor targeting.
• Utilizing pH-responsive charge reversal for endosomal escape and drug release.
• In vitro cytotoxicity assays on tumoral and non-tumoral cell lines.

Main Results:

• Gelatin-based NPs demonstrated effective intracellular drug delivery.
• The RGD motif facilitated targeting of tumor cells.
• Charge reversal mechanism promoted endosomal escape.
• Selectivity indexes greater than 30 were observed in cytotoxicity experiments, indicating high selectivity.

Conclusions:

• Gelatin-based NPs offer a dual-targeting strategy for 5-FU cancer therapy.
• The RGD motif and charge-reversal mechanism enhance therapeutic efficacy and selectivity.
• These NPs represent a promising platform for targeted intracellular drug delivery in cancer treatment.