Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer
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M Sheikh Mohamed1, Srivani Veeranarayanan1, Aby Cheruvathoor Poulose1
1Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100, Kujirai, Kawagoe, Saitama 350-8585, Japan.
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, 10-15nm 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.
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.
Insights
This study developed a dual-targeted gold nanoparticle (Au NP) therapy for aggressive gliomas. The novel nanoconjugate effectively targets cancer cells and utilizes photothermal therapy for precise ablation, halting tumor growth.
Area of Science:
- Nanomedicine
- Biotechnology
- Cancer Therapy
Background:
- Gliomas are aggressive, recurrent cancers with limited treatment options due to infiltration and metastasis.
- Developing effective therapeutic strategies for gliomas remains a significant challenge in oncology.
- Previous research has explored combination therapies to overcome treatment resistance.
Purpose of the Study:
- To develop a multifunctional nanoconjugate for targeted glioma treatment.
- To combine drug delivery and photothermal therapy for enhanced cancer cell ablation.
- To investigate the efficacy of gold nanoparticles conjugated with curcin and targeting antibodies.
Main Methods:
- Synthesized environmentally benign gold nanoparticles (Au NPs).
- PEGylated Au NPs and conjugated with folate and transferrin antibodies for dual targeting.
- Attached curcin (a ribosome inactivating protein) to Au NPs for drug delivery.
- Analyzed in vitro toxicity of curcin and photothermal properties of Au nano-conjugates.
Main Results:
- Successfully synthesized 10-15nm Au NP conjugates with high specificity for gliomas.
- Achieved pH-responsive drug release of curcin from Au NPs.
- Demonstrated curcin's toxicity via ROS generation and mitochondrial/cytoskeletal destabilization.
- Utilized gold nanoparticles' photothermal properties for precise glioma colony disruption.
Conclusions:
- The multifunctional nanoconjugate effectively arrests proliferation and migration of glioma cells.
- This nanoconjugate presents a viable multimodal treatment option for brain cancers.
- The study highlights the potential of nanomedicine in advanced cancer therapy.
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