Curcumin Bound Seleno-BSA, a Novel Bifunctional Macromolecular Therapeutic System Against A549 Lung Cancer Cells: Photophysical Characterizations, Cellular Uptake, and Efficacy.

The aim of the present study was to design a novel anticancer agent comprising of dual therapeutic moieties viz., curcumin and selenium in order to achieve synergism and consequently the better therapeutic efficacy. To this end, bovine serum albumin (BSA), a well-known transport protein was functionalized with 3,3'- diselenodipropionic acid and the resulting seleno-BSA used as the host for the physical loading with curcumin. The detailed photophysical studies established that curcumin was physically entrapped in the close proximity of tryptophan residue of the domain II of seleno-BSA with a stoichiometry of 1:1 and binding constant of 1 × 106 M-1 (by fluorescence titration). Moreover, seleno-BSA also improved the chemical stability of curcumin without undergoing any significant colloidal (hydrodynamic size and surface potential) and structural (content of secondary structures) changes. Finally, therapeutic evaluation of seleno-BSA-curcumin complex against A549 (lung cancer) cells indicated that it internalized through caveolae dependant endocytosis and induced cell killing by causing loss of mitochondrial membrane potential (MMP) and caspase-dependent apoptosis. Moreover, above study also confirmed the synergism between curcumin and seleno-BSA toward the therapeutic potency of the complex. Overall, findings of the study gain novelty for the future design of bioinspired multi-therapeutic system.