Synthesis and characterization of folic acid-conjugated human serum albumin (HSA) nanoparticles for isoalantolactone cellular uptake in HeLa

Folic acid was previously demonstrated to mediate intracellular nanoparticle uptake. Isoalantolactone (IAL) was demonstrated to possess a variety of pharmacological activities in vivo and in vitro, including cytotoxic, diuretic and immunosuppressive activity. Here, we developed folic acid-conjugated human serum albumin nanoparticles for IAL (FHNs-IAL) encapsulation to improve the targeted activity, water solubility and to reduce untoward effects.Human serum albumin nanoparticles for IAL (HNs-IAL) were prepared by desolvation and stabilized by chemical cross-linking with glutaraldehyde. Folic acid was covalently coupled to amino groups on the surface of HNs-IAL by carbodiimide reaction. The average diameter ofspherical FHNs-IAL was 118.7 ± 11.6 nm and the IAL encapsulation efficiency was 36.1 ±3.3%. The cytotoxic activity in vitro and the cellular uptake of FHNs-IAL were examined byHeLa cells. The results suggested that covalent conjugation of folic acid to HNs-IAL increased IAL uptake into cancer cells. Moreover, the cytotoxic effects of IAL as monotherapy on HeLa cells were smaller than those encapsulated with FHNs. The experiments in vivo also confirmed a superior anti-tumor effect of FHNs-IAL by human tumor xenograft animals. These data suggested that covalent linkage of folic acid could specifically increase the cellular uptake of FHNs-IAL by cancer cell. The FHNs-IAL exhibited good property to improve the uptake ofHeLa cells and could become a potential targeted drug delivery system for the future cancer chemotherapy. Therefore, folic acid-conjugated human serum albumin (HAS) nanoparticles for IAL encapsulation would be highly beneficial for biomedical and pharmaceutical applications.   Key words: Isoalantolactone, nanoparticles, serum albumin, folic acid, drug delivery system.