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Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer
Authors:M. Sheikh Mohamed  Srivani VeeranarayananAby Cheruvathoor Poulose  Yutaka NagaokaHiroaki Minegishi  Yasuhiko YoshidaToru Maekawa  D. Sakthi Kumar
Affiliation:Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100, Kujirai, Kawagoe, Saitama 350-8585, Japan
Abstract:

Background

Gliomas 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.

Methods

Gold 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.

Results

Highly cyto-compatible, 10–15 nm 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.

Conclusion

The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass.

General significance

With 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.
Keywords:Gold nanoparticle   Curcin   Glioma   Photo-thermal ablation   Dual targeting
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