ArticlePharmaceutical research2025
Active Targeting of Colorectal Cancer Using Chemotherapy-Loaded Nanoparticles Functionalized with a Folate Receptor-α (FRα) Ligand, Pemetrexed.
Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
purposeColorectal cancer (CRC) is a leading cause of cancer mortality with current chemotherapeutic strategies often limited by systemic side effects and suboptimal tumor targeting. This study aimed to enhance the delivery and efficacy of paclitaxel (PTX) for CRC therapy by engineering nanoparticles (NPs) actively targeted to the folate receptor-α (FRα) using pemetrexed, an FDA-approved antifolate with high FRα affinity.
methodsA novel FRα-targeted polymer (PLGA-PEG-pemetrexed) was synthesized by ring-opening polymerization and used to prepare tumor-targeted nanoparticles (TTNPs). The physical characteristics of TTNPs and non-targeted NPs (NTNPs) were evaluated by dynamic light scattering and TEM. Cellular uptake was assessed in FRα-expressing CT26 colorectal cancer cells by flow cytometry and confocal imaging. Cytotoxicity was evaluated using PrestoBlue™ assays. In vivo tumor targeting and therapeutic efficacy were assessed in a syngeneic CT26 tumor-bearing BALB/c mouse model using IVIS imaging, tumor accumulation and growth measurements.
resultsThe synthesized PLGA-PEG-pemetrexed formed uniform, negatively charged NPs with a hydrodynamic diameter of 140-170 nm. TTNPs demonstrated significantly enhanced uptake in FRα-expressing CT26 cells compared to NTNPs, which was abrogated by folic acid pre-treatment. In vitro, PTX-loaded TTNPs exhibited greater cytotoxicity against CT26 cells than free PTX. In vivo, TTNPs showed superior tumor accumulation compared to NTNPs, resulting in significantly greater tumor growth inhibition and increased intratumoral PTX concentrations. All treatments were well tolerated.
conclusionOur results demonstrate that active targeting of chemotherapy-loaded NPs with a FRα ligand, pemetrexed, enhances tumor targeting and antitumor efficacy in a CRC model.
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