Therapeutic Nanoparticles for Non-Viral Drug Delivery to Natural Killer Cells

Transfects Natural Killer Cells Without the Use of Viruses

These nanoparticles enable the delivery of nucleic acids or drugs to immunosuppressed natural killer (NK) cells to restore their cytotoxic functions in tumor microenvironments. Globally, cancer causes one of every six deaths, with the number of new cases expected to rise to 23.6 million per year by 2030. An important part of the human immune system, NK cells have the capacity to rapidly identify and eliminate cancerous cells in the body. However, solid tumors often develop an immunosuppressive microenvironment that inhibits the infiltration and cytotoxic functions of these NK cells. Other available technologies can deliver nucleic acids to the NK cells in order to reactivate their cytotoxic abilities, but they require using viral vectors as the method of delivery. NK cells are notoriously difficult to genetically manipulate, and even viral vectors and remain inefficient.

Researchers at the University of Florida have developed manganese dioxide nanoparticles that serve as a non-viral drug delivery system for NK cells in order to restore their cancer-killing functions. These nanoparticles transfect the NK cells without any additional physical assistance, such as magnetic stimulation or electroporation.

Application

Intracellular drug delivery system that uses nanoparticles to transfect natural killer cells

Advantages

• The nanoparticles can be used for ex vivo manipulation of NK cells for enhanced adoptive cell therapies, as well as for in vivo tumor targeting and activation of resident NK cells.
• Enables intracellular nucleic acid and drug delivery to natural killer cells, reactivating their anti-tumor function in immunosuppressive tumor microenvironments
• Modifies a tumor’s hypoxic environment, speeding up the decomposition of hydrogen peroxide
• The nanoparticles are successfully taken up by NK cells without requiring additional particle uptake procedures, thereby simplifying the ex vivo manipulation of NK cells without compromising their viability.

Technology

The nanoparticles are composed of manganese dioxide, which catalyzes the breakdown of hydrogen peroxide to form oxygen and water. This serves to protect NK cells from oxidative stress generated in the hypoxic tumor microenvironment. Additionally, these nanoparticles facilitate the delivery of reactivating drugs and nucleic acids, specifically DNA and RNA molecules, to immunosuppressed natural killer cells to restore their anticancer immune functions. A cationic surface polymer can form a complex with DNA and RNA to deliver them into NK cells. The NK cells readily uptake these molecules and other medicinal compounds. For example, a nanoparticle complex with a silencing RNA will silence the transforming growth factor beta (TGF-β) cytokine, which cancer cells produce to inhibit NK cells. This combination of oxidative stress modification and TGF-β silencing promotes the reactivation of NK cells within a tumor microenvironment, inducing an immunotherapeutic response.