Cryptolepine-transferrin nanosystem preparation and the anticancer effects on human malignant glioblastoma U87MG...

In this study, the synthesis and characterization of the human transferrin (hTf)-cryptolepine complex nanostructure were performed. The interaction of hTf in the forms of native and nanostructures with cryptolepine was evaluated through various spectroscopic methods, molecular docking, and molecular dynamic (MD) simulation studies. Finally, the anticancer mechanisms of the prepared complex nanostructure on the Human malignant glioblastoma U87MG cell line and normal astrocytes were assessed using cell viability, RT-PCR, and ELISA assays. The data showed that hTf and hTf-cryptolepine complex nanostructures exhibited particle sizes of 149.37 ± 28.98 and 161.85 ± 33.44 nm, and average zeta potential values of -11.85 ± 1.98 and -23.87 ± 2.202 mV, respectively. It was also found that the drug release behavior from the hTf-cryptolepine complex nanostructures displayed a pH-sensitive pattern, demonstrating a strong correlation with the Higuchi model and a moderate correlation with the Korsmeyer-Peppas model. Spectroscopy and MD simulation studies revealed that the interaction of hTf and cryptolepine did not induce significant changes in the structure of the protein. Moreover, binding parameters were determined to be greater for hTf-cryptolepine complex nanostructures compared to the hTf-cryptolepine complex. Cellular assays showed that the calculated IC₅₀ concentrations of cryptolepine, hTf-cryptolepine complex, and hTf-cryptolepine complex nanostructures in Human malignant glioblastoma U87MG cells were 16.1, 14.31, and 4.60 μM, respectively. Furthermore, it was demonstrated that Human malignant glioblastoma U87MG cells treated with hTf-cryptolepine complex nanostructures had a more significant increase in caspase-3 expression and activity compared to free cryptolepine or the hTf-cryptolepine complex. In conclusion, this paper may hold great promise for the introduction of bionanotherapeutics, which require further evaluation in future studies.