Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer

Abstract

BackgroundGliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. MethodsGold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. ResultsHighly cyto-compatible, 10–15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. ConclusionThe multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. General significanceWith multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.