Selection of superior targeting ligands using PEGylated PLGA nanoparticles for delivery of curcumin in the treatment of triple-negative breast cancer cells

Many chemotherapeutic drugs are unable to achieve their potency because of their hydrophobic nature [e. g. curcumin (Cur)], coupled to its inability to reach the target site, lower circulation time and low half-lifetime. To overcome these, PLGA nanoparticles were synthesized, loaded with curcumin, coated with polyethylene glycol (PEG) and conjugated with different targeting moieties - either folic acid (FA), or hyaluronic acid (HA), or transferrin (Tf) - in the quest to find the best possible targeting agent. TEM images confirm uniform coating of PEG over the PLGA nanoparticle surface, with a size increment from 85 nm (for only PLGA) to ~124 nm (for PLGA-Cur-PEG-ligand nanoparticles), subsequent to PEG coating and attachment of targeting moieties. Cell viability experiments at 80 μM drug concentration on MDA-MB-231 cells confirmed that, viability gradually decreased from 92% to 41%, 32%, 39%, 19% and 8% for free Cur in PBS, to PLGA-Cur, PLGA-Cur-PEG, PLGA-Cur-PEG-Tf, PLGA-Cur-PEG-HA and PLGA-Cur-PEG-FA, respectively. Confocal microscopy and flow cytometry established a higher percentage of curcumin internalization in cells, leading to enhanced cancer cell killing with targeted nanoparticles. Therefore, HA and FA ligands are better targeting moieties, to treat highly aggressive and metastatic MDA-MB-231 breast cancer cells using PLGA nanoparticles.