Precision nanomachines deliver gene therapy to lymph nodes, suppressing breast cancer spread

Sentinel lymph nodes (SLNs) serve as the first checkpoint in breast cancer metastasis and play a crucial role in halting cancer progression.

However, in advanced cancers with metastatic potential, cytotoxic CD8-positive T cells, which are supposed to attack cancer cells, are inactivated through the protein TGF-?1 secreted by cancer cells in the SLN.

Collaborative research of the The Innovation Center of NanoMedicine with Professor Kanjiro Miyata's group from the Department of Materials Engineering/Bioengineering at the Graduate School of Engineering, The University of Tokyo aimed to reactivate these cytotoxic CD8-positive T cells to suppress the recurrence and metastasis of breast cancer.

Specifically, nanomachines were strategically designed to deliver antisense nucleic acid (ASO) aimed at lowering the expression level of TGF-?1 in the SLN.

Generally, biological tissues, including lymph nodes, have fine mesh structures, requiring the preparation of drugs or drug delivery systems that can pass through these structures. Compared to the vascular system, delivering drugs via the lymphatic system poses greater challenges. For example, lipid nanoparticles used in COVID-19 vaccines are approximately 100 nm in size, a relatively large size that might hinder their entry into lymph nodes.

In contrast, the research team successfully created "dynamic nanomachines" that are 10 nm in size, capable of loosely encapsulating ASOs to efficiently deliver them to SLNs and effectively engage with target immune cells.

Image source: Miyata Lab, University of Tokyo.