New Folate-modified Human Serum Albumin Conjugated to Cationic Lipid Carriers for Dual Targeting of Mitoxantrone against Breast Cancer

Aims: In the present work, folic acid-modified human serum albumin conjugated to cationic solid lipid nanoparticles were synthesized as nanocarriers of mitoxantrone for the treatment of breast cancer. Background: Dual-targeted drug delivery is a new drug dosing strategy that is frequently used to enhance the therapeutic efficacy of anticancer drugs. Objective: Dual targeting of the cancer cells was achieved by dual tagging of human serum albumin and folic acid on the surface of the lipid nanoparticles. Methods: The targeted drug-loaded nanocomplexes were synthesized and characterized using transmission electron microscopy along with photon-correlation and Fourier-transform infrared spectroscopic techniques. The anti-cancer activity of the nanocomplexes was screened against an in-vitro model of MCF-7 and MDA-MB-231 breast cancer cell lines to examine drug efficacy. Results: The entrapment efficiency and drug loading values for mitoxantrone were calculated to be 97 and 8.84%, respectively. The data from the drug release studies for the system indicated the release profile did not significantly change within a pH range of 5.5-7.4. The hemolysis ratio of the hybrid carrier was less than 5% even at the upper doses of 3 mg/mL, demonstrating its safety for intravenous injection with limited hemolysis and a long blood circulation time. Conclusion: The cell cytotoxicity results confirmed that the drug hybrid nanocomplex was more toxic to breast cancer cells compared with the free drug. Furthermore, the weakly cationic and small size particles prevented opsonin binding of nanocomplexes, improving blood circulation time and cancer tissue uptake.