Folate Receptor-Targeted Camptothecin-Loaded PLGA-Glutenin Nanoparticles for Effective Breast cancer Treatment

Abstract

The combination of natural and synthetic polymers for nanomedicine development had many advantages, including less toxicity, biocompatibility, prolonged circulation, higher stability, and ease of surface modification. Here, a novel folic acid-conjugated Camptothecin-loaded-poly (lactic-co-glycolic) acid-glutenin nanoparticles (FA-CPT-PLGA-Glu NPs) was fabricated to treat breast cancer. FA-CPT-PLGA-Glu NPs target breast cancer cells via upregulated folate receptors and delivered their toxic payloads without disrupting healthy cells. First, CPT-loaded PLGA NPs were created using a modified emulsification/evaporation technique. Second, Glu-based CPT-PLGA NPs were synthesized using a layer-by-layer assembly, and their physiochemical properties were validated. CPT encapsulation efficiency and loading capacity into PLGA-Glu NPs were 74.95 ± 1.34% and 4.78 ± 1.08%, respectively. CPT-PLGA-Glu NPs exhibited sustained and controlled release of loaded-CPT from NPs, and the highest content was released in an acidic environment (pH 5.3), which will be advantageous for cancer treatment. Later, FA-CPT-PLGA-Glu NPs were synthesized by simple conjugation chemistry. The fabricated FA-CPT-PLGA-Glu NPs were around 100 nm in size, with a spherical form and crystalline nature. FA-CPT-PLGA-Glu NPs show strong cytotoxicity activity, and its IC₅₀ value was 16.33 µg × mL^− 1 against breast cancer cell line (MCF-7). This folate-receptor-targeted NPs are more effectively internalized into MCF-7 cells, causing ROS generation, cell growth inhibition, and apoptosis. The activity of caspase-3 and − 9 causes MCF-7 cells apoptosis by internalized CPT. Further, internalized CPT induces potential loss of mitochondrial transmembrane and damages the nuclear integrity of the cancer cells. These results showed that the FA-CPT-PLGA-Glu NPs target upregulated folate receptors on the surface of MCF-7 cells.

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