Transient Receptor Potential (TRP) Ion Channel - Dependent Toxicity of Silica Nanoparticles and Poly(amido amine) (PAMAM) Dendrimers.

Fundamental to the design and development of nanoparticles for applications in nanomedicine is a detailed understanding of their biological fate and potential toxic effects. Transient receptor potential (TRP) ion channels are a large superfamily of cation channels with varied physiological functions. This superfamily is classified into six related subfamilies; TRPC (canonical), V (vanilloid), M (melastatin), A (ankyrin), P (polycystin) and ML (mucolipin). TRPA1, M2 and M8 are nonselective Ca2+-permeable cation channels which regulate calcium pathways under oxidative stress. Some of these channels are highly expressed in immune cells where they can regulate cytokine production and inflammatory responses. Using a series of well characterized silica nanoparticles with variations in size (approximately 50-350 nm in diameter) and porosity, as well as cationic and anionic poly(amido amine) (PAMAM) dendrimers of similar size, we examined the toxicity of these nanoparticles to HEK-293 cells overexpressing different TRP channels. Our data shows that the toxicity of smaller and mesoporous silica nanoparticles was influenced by expression of the TRPM2 and TRPM8 channels, while only mesoporous SiNPs showed TRPA1-related toxicity. Additionally, TRPA1 and TRPM2 played a role in the toxicity of cationic dendrimers, but not for anionic dendrimers. TRPV4 does not seem to play a significant role in silica nanoparticle or PAMAM toxicity.