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.

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.