Amphiphilic Poly(γ‐glutamic acid) Derivatives for Delivering Doxorubicin in Cancer Cells

One of the most limiting factors in cancer treatment is the difficulty of delivering anticancer agents effectively to tumor sites. To overcome this challenge, this research focuses on developing a carrier that has been modified to possess amphiphilic properties while remaining biodegradable and biocompatible. Amphiphilic esters derived from poly(γ-glutamic acid) by modifying the carboxylate side groups with 4-phenyl-butyl bromide were prepared. These copolymers self-assembled into nanoparticles via nanoprecipitation. The cytocompatibility of the nanoparticles was assessed through lactate dehydrogenase release and metabolic activity of U-87 glioma cells. Fluorescein isothiocyanate labeling demonstrated effective cellular uptake of nanoparticles. These nanoparticles were further decorated with polyethylene glycol (PEG) and a PEG-folic acid conjugate (FA-PEG-NH₂), their sizes being 174 and 156 nm, respectively. Successful grafting was confirmed through ¹H-NMR and FTIR spectroscopy. The nanoparticles were loaded with doxorubicin, and release studies showed their sensitivity to the pH of the environment, the encapsulated drug being released faster at pH 4.2 compared to pH 7.4. Encapsulated doxorubicin's effect on U-87 cells was tested at various concentrations and time points, showing significantly better performance compared to free doxorubicin. These results suggest that those poly(γ-glutamic acid) derivatives hold great promise for improving the delivery of hydrophobic drugs and enhancing cancer treatment.