Smart Tumor Cell-Derived DNA Nano-Tree Assembly for On-Demand Macrophages Reprogramming

Area of Science:

• Biomedical Engineering
• Immunology
• Nanotechnology

Background:

• Antitumor immunotherapy efficacy is limited by the imbalance between tumor cells and tumor-associated macrophages (TAMs).
• Targeting TAM polarization is crucial for effective cancer treatment.

Purpose of the Study:

• To develop a smart, on-demand strategy for regulating TAMs using tumor cell-derived signals.
• To investigate the potential of a DNA nanostructure-based approach for cancer immunotherapy.

Main Methods:

• A proximity-anchored non-linear hybridization chain reaction (Panel-HCR) strategy was designed.
• The Panel-HCR system utilizes DNA nanostructures to recognize tumor cells and release CpG oligodeoxynucleotides (CpG-ODNs).
• Tumor cell-targeted bioimaging was performed in vitro, in tissues, and in vivo.

Main Results:

• The Panel-HCR strategy successfully assembled DNA nanostructures on tumor cell surfaces.
• On-demand release of CpG-ODNs was achieved, dependent on tumor cell concentration.
• CpG-ODNs effectively converted M2 TAMs to the M1 phenotype, activating the NF-κB pathway and increasing inflammatory cytokines.
• Significant antitumor immune responses were observed in vitro and in vivo.

Conclusions:

• The Panel-HCR strategy offers a promising approach for on-demand regulation of TAMs in cancer immunotherapy.
• This method demonstrates potential for improving the clinical benefits of antitumor immunotherapies.