Smart nanoparticles deliver mRNA to tumors, reprogramming immune cells

September 16, 2026 at 01:30 PM1 min

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University of Adelaide researchers developed smart nanoparticles that deliver mRNA directly to tumor-associated macrophages, reprogramming them to recruit T cells. The nanoparticles carry mRNA encoding CXCL9 and the immune-stimulating drug resiquimod. In laboratory tests, treated macrophages showed an 89.5-fold increase in NOS2 expression, indicating immune activation.

Key Facts

The study was published this week in Science Advances.
The smart nanoparticles are studded with antibodies that bind to TREM2, a protein on tumor-associated immunosuppressive macrophages.
The mRNA carries instructions for producing CXCL9, a chemical signal that recruits T cells.
The nanoparticles also carried resiquimod, a drug that stimulates certain immune pathways.
Expression of NOS2, a marker of active immune state, increased by a factor of 89.5 in treated macrophages.

Tumor Microenvironment Challenge

Tumors create an environment that suppresses cancer-fighting immune cells, sometimes reprogramming them to hinder other parts of the immune system. Tumor-associated macrophages, when rewired by cancer signals, block the arrival and activity of T cells, one of the body's main anti-cancer weapons. University of Adelaide professor Chunxia Zhao said the tumor environment can stop immune cells from attacking the tumor.

Smart Nanoparticle Delivery System

The researchers developed a delivery method they dubbed 'smart' nanoparticles to ensure the mRNA reached only the tumor site. The nanoparticles are encased in a lipid envelope, similar to standard mRNA therapies, but with added targeting antibodies. The antibodies bind to TREM2, a protein present on the surface of tumor-associated immunosuppressive macrophages. This targeting mechanism ensures the therapy reaches only macrophages in the tumor region that need reprogramming.

Laboratory Results

Initial laboratory results showed that previously lethargic macrophages began producing CXCL9 and other markers of an active immune state. Expression of NOS2 increased by a factor of 89.5 in treated macrophages. Signals of a more immunosuppressive state notably decreased after treatment.