Supramolecular nanoassembly of lysozyme and α-lactalbumin (apo α-LA) exhibits selective cytotoxicity and enhanced bioavailability of curcumin to cancer cells.

Hybrid supramolecular spherical nanoassembly of hen egg white lysozyme and bovine apo α lactalbumin (SN) was prepared with a mean size of ˜55.2 nm using an optimized desolvation method via chemical crosslinking. The nanoassembly, SN demonstrated dose-dependent reactive oxygen species (ROS) mediated cytotoxicity in multiple cancer cells such as MCF-7, MDA-MB231, HeLa and MG 63. It also demonstrated high loading capacity of a phytochemical based anticancer agent, curcumin (248.8 mg/g) and target-based pH-responsive in vitro drug release with around 85.8% curcumin release observed under acidic condition. Moreover, curcumin loaded SN (SN-CUR) induced cell viability reduction in all cancer cells including mouse melanoma (B16F10) by more than 90% within 24 h. Further, SN and SN-CUR when conjugated with folic acid enhanced the cytotoxicity via folate receptor-based targeting. Both drug loading and release induced conformational change and folding reconstitution of the protein nano-assembly, respectively, which made the whole system an efficient therapeutic agent that works via a dual mode of action. We demonstrated that SN and SN-CUR were highly biocompatible in vitro. Therefore, our supramolecular protein nanoassembly loaded with curcumin could emerge as a comprehensive cancer therapeutics that acts via a strategic mode of dual therapeutic mechanisms.