Hybrid supramolecular spherical nanoassembly of hen egg white lysozyme and bovine apo α lactalbumin (SNLYZ-BLA) was prepared with a mean size of ˜55.2 nm using an optimized desolvation method via chemical crosslinking. The nanoassembly, SNLYZ-BLA 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 SNLYZ-BLA (SNLYZ-BLA-CUR) induced cell viability reduction in all cancer cells including mouse melanoma (B16F10) by more than 90% within 24 h. Further, SNLYZ-BLA and SNLYZ-BLA-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 SNLYZ-BLA and SNLYZ-BLA-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.
Keywords: Anti-cancer activity; Bioavailability; Oxidative stress; Supramolecular protein nanoassembly; Targeted therapy.
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