Green synthesis of lignin-based nanoparticles as a bio-carrier for targeted delivery in cancer therapy

Polymeric magnetic nanoparticles have shown higher efficacy in cancer diagnosis and treatment than conventional chemotherapies. Lignin is an abundantly available natural polymer that can be selectively modified using a rapidly expanding toolkit of biocatalytic and chemical reactions to yield 'intelligent' theranostic-nanoprobes. We aim to valorize lignin to develop a natural polymeric-magnetic-nano-system for the targeted delivery of methotrexate. In the current study, we synthesized nanoparticles of lignin and iron oxide with methotrexate using a new approach of anti-solvent precipitation with ultrasonication. The ensuing nanoparticles are magnetic, smooth, polyhedral with characteristic dimension of 110-130 nm. The drug loading and encapsulation efficiencies were calculated to be 66.06 % and 64.88 %, respectively. The nanoparticles exhibit a concentration-dependent release of methotrexate for the initial 24 h, followed by sustained release. Moreover, formulation is non-hemolytic and scavenges radicals owing to the antioxidant property of lignin. Additionally, methotrexate delivered using the nanoparticles exhibited higher cytotoxicity in cellular-viability assays employing breast cancer and macrophage cell lines compared to the pure form of the drug. Synergistic action of lignin, iron oxide, and methotrexate contribute to enhanced caspase-3 activity and reduced glutathione levels in the breast cancer cells, as well as elevated internalization of the drug on account of increased receptor-mediated endocytosis.