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Stable DNA Motifs, 1D and 2D Nanostructures Constructed from Small Circular DNA Molecules
Published on: April 12, 2019
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Blood-declustering excretable metal clusters assembled in DNA matrix.
Jaiwoo Lee1, Quoc-Viet Le2, Seungbeom Ko1
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Biomaterials
|September 4, 2022
Summary
Polymeric DNA-supported gold nanoclusters (AuPCN) effectively treat tumors via enhanced light-to-heat conversion and immune stimulation. These nanoclusters decluster in the bloodstream, reducing long-term retention and improving safety.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Immunotherapy
Background:
- Gold nanoclusters offer potential in photothermal therapy and drug delivery.
- Developing safe and effective nanomedicines requires strategies to manage in vivo circulation and clearance.
- Immunostimulatory DNA, like polyCpG DNA, can activate anti-tumor immune responses.
Purpose of the Study:
- To develop and characterize polyCpG DNA-supported gold nanoclusters (AuPCN) for cancer immunotherapy.
- To investigate the in vivo behavior, therapeutic efficacy, and safety profile of AuPCN.
- To evaluate the potential of DNA scaffolds for designing declusterable nanomedicines.
Main Methods:
- Synthesis and characterization of polyCpG-supported gold nanoclusters (AuPCN) and monomer CpG-bound gold nanoparticles (AuMC).
- Assessment of interparticle plasmon-coupling and light-to-heat conversion efficiency.
- In vivo studies in CT26 tumor-bearing mice, including therapeutic efficacy, immune cell infiltration, and biodistribution/excretion analysis.
Main Results:
- AuPCN exhibited interparticle plasmon-coupling and superior light-to-heat conversion compared to AuMC.
- AuPCN declustered into subunits in serum, while AuMC remained intact.
- AuPCN treatment combined with near-infrared irradiation (AuPCN(+NIR)) resulted in 100% survival and 0% tumor recurrence in mice, with enhanced cytotoxic and memory T cell responses.
- Urinary excretion of gold was observed in the AuPCN-treated group, indicating efficient clearance.
Conclusions:
- Polymeric DNA-supported gold nanoclusters (AuPCN) demonstrate significant anti-tumor efficacy and potent immunotherapeutic effects.
- The declustering property of AuPCN in the bloodstream enhances safety by facilitating clearance.
- This DNA scaffold-based approach offers a promising strategy for developing declusterable metal nanoclusters for biomedical applications.
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