Folic Acid Conjugated Amino Acid-Based Star Polymers for Active Targeting of Cancer Cells

Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L-cystine)(core)) with peripheral allyl functionalities were synthesized by sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAS) via the arm-first approach, using N-(trimethylsilyl) allylamine as the initiato. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic acid conjugate via thiolene click chemistry afforded poly (PEG-b-L-lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with folic acid targeting moieties. Similarly, a contol was prepared without folic acid, using just PEG. A fluorophore was used to track both star polymers incubated with breast cancer cells (MDA-MB-231) in vitro. Confocal microscopy and flow cytometry, revealed that the stars could be internalized into the cells, and higher cell internationalizaion was observed when folic acid moieties were present. Cytotoxicity as studies indicate that both stars are nontoxic to MDA-MB-231 cells at concentrations of up to 50 mu g/mL. These results make this amino acid-based star polymer an attractive candidate in targeted drug delivery applications including chemotherapy.