Bioinspired synthesis of ultra-small copper-aspartate BioMOF nanodots using sodium caseinate for targeted curcumin delivery

In this study, an attempt was made to create of copper-aspartate (Cu-Asp) biological metal organic framework (bioMOF), inspired by the process of bio-mineralization. Ultra-small nanodots of biocompatible Cu-Asp was synthesized as a carrier for curcumin (CCM) in the presence of sodium caseinate (CAS) in an aqueous medium at room temperature. Synthesis was performed in the presence of different amounts of CCM (10, 15, and 20 mg). Two different morphologies of the nanorod and nanodots (for the first time) were obtained. To target the drug delivery processes, the folic acid (FA) factor was used during the synthesis of ultra-samll nanodots. X-ray diffraction, scanning and field emission scanning (SEM and FESEM) and transmission electron microscopies, Fourier transform infrared (FT-IR), UV-Vis, and Thermogravimetric (TG) analyses were performed to characterize the synthesized nanostructures. The drug loading efficiency and capacity percentages for CAS/CCM/FA@Cu-Asp (5.1 and 74%, respectively) indicated that the encapsulation of the drug was appropriate. In addition, the rate of drug release at different pH values was investigated, and the results showed different performances of the nanocarriers at pH = 5.5, 6.8, and 7.4. The release of CCM from CAS/CCM@Cu-Asp was 60% at pH = 5.5 after 3 days. At pH 7.4, only 10% CCM was released after 4 h and remained nearly stable. The potential cytotoxicity was evaluated using the MTT assay in Normal skin fibroblast and HeLa (positive folate receptor cancer cell) cell lines. The highest SI was observed for CAS/CCM/FA@Cu-Asp (2.15).