Riboflavin-targeted polymers improve tolerance of paclitaxel while maintaining therapeutic efficacy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Active targeting enhances drug delivery systems (DDS) efficacy in cancer treatment.
• Riboflavin (RF) is a biocompatible ligand with high cancer cell receptor expression, suitable for active targeting.
• Paclitaxel (PTX) is a potent chemotherapy drug with significant systemic toxicity.

Purpose of the Study:

• To evaluate RF-targeted PEG-PTX nanoparticles (PEG PTX RF) as a DDS for cancer therapy.
• To compare the efficacy and toxicity of targeted versus non-targeted DDS in vitro and in vivo.
• To assess the impact of RF targeting on drug uptake and therapeutic outcomes.

Main Methods:

• Synthesis of RF-conjugated 4-arm polyethylene glycol (PEG) stars with Paclitaxel (PTX).
• In vitro cytotoxicity assays comparing PEG PTX RF, PEG PTX, and free PTX against tumor cells.
• In vivo studies in tumor-bearing animals to evaluate treatment efficacy, tumor proliferation, and systemic toxicity.

Main Results:

• PEG PTX RF demonstrated higher in vitro toxicity against tumor cells than non-targeted PEG PTX.
• In vivo, all treatments showed similar efficacy, but PEG PTX RF resulted in reduced tumor cell proliferation, indicating sustained effects.
• Targeted and non-targeted DDS mitigated PTX's adverse effects on animal body and liver weights compared to free PTX.

Conclusions:

• RF-targeted DDS (PEG PTX RF) effectively deliver PTX to cancer cells, enhancing drug uptake and enabling sustained therapeutic effects.
• The developed DDS significantly reduces the systemic toxicity associated with PTX chemotherapy.
• Active targeting with RF offers a promising strategy for improving the precision and safety of cancer drug delivery.