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Updated: Oct 17, 2025

Gene-therapy Inspired Polycation Coating for Protection of DNA Origami Nanostructures
Published on: January 19, 2019
DNA Origami Frameworks Enabled Self-Protective siRNA Delivery for Dual Enhancement of Chemo-Photothermal Combination
Tingting Xu1, Sha Yu1,2,3, Yao Sun1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210023, P. R. China.
Abstract:
Although chemotherapy and photothermal therapy are widely used to combat cancer, their efficacy is often limited by multidrug resistance. Small interfering RNAs (siRNAs) have ability to suppress the expression of target genes, which has been extensively employed for combating the multidrug resistance to chemodrugs and hyperthermia in cancer therapy. However, efficient delivery of siRNAs along with chemo-photothermal agents in vivo is still an enormous challenge. Herein, octahedral DNA origami frameworks (OctDOFs) are constructed as a nanovehicle for precise organization and orchestrated delivery of siRNAs, chemodrugs (doxorubicin, Dox), and photothermal agents (gold nanorods, AuNRs) in combinatorial treatment of cancer. The inner cavity of the rigid OctDOFs structure is able to shield the encapsulated siRNAs during transportation by sterically hindering RNase degradation and protein binding, thus achieving effective downregulation of connective tissue growth factor (CTGF) and heat shock protein 72 (HSP72) for dual sensitization of cancer cells to chemodrugs and hyperthermia. By amplifying chemo-photothermal therapeutic potency with siRNAs, the proposed OctDOFs exhibited superior cytotoxicity and tumor inhibition efficacy in vitro and in vivo. This nanovehicle creates a promising siRNA delivery platform for precise medication and combination therapy.
Insights
Octahedral DNA origami frameworks deliver small interfering RNAs (siRNAs), chemotherapy drugs, and photothermal agents to overcome cancer multidrug resistance. This combination therapy enhances treatment efficacy both in vitro and in vivo.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Chemotherapy and photothermal therapy face limitations due to multidrug resistance in cancer treatment.
- Small interfering RNAs (siRNAs) show potential in combating multidrug resistance but face delivery challenges.
- Efficient co-delivery of siRNAs with therapeutic agents remains a significant hurdle in cancer therapy.
Purpose of the Study:
- To develop a novel nanovehicle for the precise organization and orchestrated delivery of siRNAs, chemotherapy drugs, and photothermal agents.
- To investigate the potential of octahedral DNA origami frameworks (OctDOFs) as a platform for combinatorial cancer therapy.
- To enhance the efficacy of cancer treatment by overcoming multidrug resistance through synergistic effects.
Main Methods:
- Octahedral DNA origami frameworks (OctDOFs) were constructed as nanovehicles.
- OctDOFs were loaded with small interfering RNAs (siRNAs), doxorubicin (Dox), and gold nanorods (AuNRs).
- The delivery system's efficacy was evaluated in vitro and in vivo for cancer treatment.
Main Results:
- OctDOFs successfully encapsulated and protected siRNAs from degradation, enabling effective downregulation of CTGF and HSP72.
- The nanovehicle facilitated dual sensitization of cancer cells to chemotherapy and hyperthermia.
- Enhanced cytotoxicity and tumor inhibition were observed in vitro and in vivo, demonstrating superior therapeutic outcomes.
Conclusions:
- Octahedral DNA origami frameworks serve as a promising nanocarrier for combinatorial cancer therapy.
- This platform enables precise delivery of multiple therapeutic agents, overcoming multidrug resistance.
- The developed nanovehicle offers a potential strategy for advanced and effective cancer treatment.
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