An _epH-driven DNA nanodevice for impeding metastasis in vivo by selectively blocking cell signaling

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• Cancer metastasis is a major cause of cancer mortality.
• Current antimetastatic treatments lack targeted therapeutic options.
• Synthetic-receptor toolkits show potential but have not yet suppressed metastasis in vivo.

Purpose of the Study:

• To develop the first extracellular pH (pHe)-driven DNA nanodevice for in vivo antimetastatic treatment.
• To manipulate heterogeneous receptors on tumor cell surfaces for therapeutic effect.
• To suppress tumor metastasis by targeting the hepatic growth factor (HGF)/c-Met signaling pathway.

Main Methods:

• Constructed a DNA nanodevice with receptor-specific aptamers locked by i-motifs.
• Utilized acidic extracellular pH to induce dynamic nanodevice reassembly.
• Demonstrated nanodevice-induced oligomerization of c-Met and transferrin receptor.

Main Results:

• The nanodevice effectively inhibited tumor metastasis in vivo.
• Achieved an 86.25% suppressive efficacy in a hepatocarcinoma-pulmonary-metastasis mouse model.
• Successfully blocked the hepatic growth factor (HGF)/c-Met signaling pathway.

Conclusions:

• The developed DNA nanodevice represents the first pHe-driven system for in vivo antimetastatic therapy.
• This approach demonstrates significant potential for adaptive antimetastatic therapeutics.
• The nanodevice's ability to manipulate cell surface receptors offers a new paradigm in cancer treatment.