DNA-Engineered Degradable Invisibility Cloaking for Tumor-Targeting Nanoparticles.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Nanoparticle (NP) delivery systems are crucial for cancer therapy and vaccines.
• Liver sequestration of NPs significantly hinders targeted delivery efficiency.
• Overcoming liver phagocytosis is essential for effective in vivo nanoagent delivery.

Purpose of the Study:

• To develop a DNA-engineered strategy to circumvent liver phagocytosis.
• To enhance tumor-targeted delivery of nanoagents using a novel cloaking method.
• To investigate the potential of DNA-engineered invisibility cloaking (DEIC) for theranostic applications.

Main Methods:

• Coating NPs with a DNA monolayer to adsorb dysopsonin proteins and induce liver invisibility.
• Utilizing the tunable degradation of DNA shells in vivo to trigger tumor-specific uptake.
• Evaluating DEIC using Ag2S quantum dots and nanoliposomes in mouse models.
• Employing near-infrared-II imaging to quantify tumor-to-liver delivery ratios.

Main Results:

• The DNA monolayer on NPs preferentially adsorbed serum dysopsonin proteins, rendering them functionally invisible to the liver.
• Tumor-specific uptake was achieved through the in vivo degradation of the DNA shell, with tunable degradation rates.
• DEIC demonstrated efficacy in both Ag2S quantum dot and nanoliposome systems.
• Near-infrared-II imaging showed a high tumor-to-liver ratio of up to ~5.1, an 18-fold improvement over conventional nanomaterials.

Conclusions:

• DNA-engineered invisibility cloaking (DEIC) effectively circumvents liver sequestration of NPs.
• This approach significantly enhances tumor-targeted delivery of nanoagents in vivo.
• DEIC offers a potentially universal strategy for high-efficiency targeted delivery of theranostic agents.