Ceramic Nanoparticles Deliver Genes to the Spleen, Trigger Antitumor Immune Response
A detailed comparison of different types of ceramic nanoparticles has found that those made of silica can efficiently transport therapeutic genes to the spleen and trigger a potent immune response capable of attacking tumors. This work, led by Kam Hui, Ph.D., of the National Cancer Centre in Singapore, appears in the journal Gene Therapy.
Working with ceramic nanoparticles made of silica, hydroxyapatite (the mineral that makes up bone), and zirconia, the investigators studied the effect of charge and surface coating on the efficiency with which these nanoparticles could deliver DNA to the nucleus of cells. These experiments revealed that silica particles coated with protamine sulfate, a naturally occurring, positively charged protein used to treat anticoagulant overdoses, had the best combination of physical characteristics to function as gene delivery vehicles.
After optimizing the protamine-coated silica nanoparticles for DNA delivery to cells, the investigators loaded the particles with a gene that codes for the firefly protein luciferase. Within 24 hours after injecting these particles into mice, the researchers found high levels of gene expression in the spleens of the treated mice, with little gene expression occurring in the liver or kidneys. Microscopy studies showed that only the spleen accumulated measurable levels of the injected nanoparticles, suggesting to the researchers that they had developed a spleen-specific gene delivery system.
Since the spleen plays a critical role in the initiation of an immune response, the investigators decided to see if they could use their protamine-coated silica nanoparticles to trigger an antitumor immune response against a cancer-related protein. To test this hypothesis, the investigators created a gene construct that, if expressed in the spleen, should produce a hybrid protein that might trigger such a response. Indeed, when the researchers loaded this gene construct onto the silica nanoparticle and injected it repeatedly into tumor-bearing mice, they observed a robust immune response that stopped tumor growth.
This work is detailed in the paper "Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen." An abstract of this paper is available through PubMed.