Active Targeting of Colorectal Cancer Using Chemotherapy-Loaded Nanoparticles Functionalized with a Folate Receptor-α...

Area of Science:

• Nanomedicine
• Oncology
• Drug Delivery

Background:

• Colorectal cancer (CRC) poses a significant mortality risk, with current treatments facing challenges in systemic side effects and tumor targeting.
• Developing advanced drug delivery systems is crucial for improving CRC therapeutic outcomes.

Purpose of the Study:

• To engineer paclitaxel (PTX)-loaded nanoparticles (NPs) actively targeted to folate receptor-α (FRα) for enhanced colorectal cancer (CRC) therapy.
• To utilize pemetrexed, an FDA-approved antifolate with high FRα affinity, as a targeting ligand for NPs.

Main Methods:

• Synthesized a novel FRα-targeted polymer (PLGA-PEG-pemetrexed) for creating tumor-targeted nanoparticles (TTNPs).
• Evaluated NP characteristics, cellular uptake in FRα-expressing CT26 cells, in vitro cytotoxicity, and in vivo tumor targeting and efficacy in a mouse model.

Main Results:

• TTNPs exhibited enhanced cellular uptake and greater cytotoxicity against CT26 cells compared to non-targeted NPs (NTNPs).
• In vivo studies demonstrated superior tumor accumulation, significant tumor growth inhibition, and increased intratumoral PTX concentrations with TTNPs.
• All treatments were well tolerated, indicating a favorable safety profile.

Conclusions:

• Active targeting of chemotherapy-loaded NPs using pemetrexed as an FRα ligand significantly improves tumor targeting and antitumor efficacy in a colorectal cancer model.
• This strategy offers a promising approach to overcome limitations of conventional CRC chemotherapy.