RT Journal Article
SR Electronic
T1 Transient Receptor Potential Ion Channel–Dependent Toxicity of Silica Nanoparticles and Poly(amido amine) Dendrimers
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 751
OP 760
DO 10.1124/jpet.118.253682
VO 370
IS 3
A1 Mohammadpour, Raziye
A1 Yazdimamaghani, Mostafa
A1 Reilly, Christopher A.
A1 Ghandehari, Hamidreza
YR 2019
UL http://jpet.aspetjournals.org/content/370/3/751.abstract
AB Fundamental to the design and development of nanoparticles for applications in nanomedicine is a detailed understanding of their biologic fate and potential toxic effects. Transient receptor potential (TRP) ion channels are a large superfamily of cation channels with varied physiologic functions. This superfamily is classified into six related subfamilies: TRP canonical, TRP vanilloid (TRPV), TRP melastatin (TRPM), TRP ankyrin (TRPA), TRP polycystin, and TRP mucolipin. TRPA1, TRPM2, and TRPM8 are nonselective Ca2+-permeable cation channels which regulate calcium pathways under oxidative stress, whereas TRPV4 can be activated by oxidative, osmotic, and thermal stress as well as different fatty acid metabolites. 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 human embryonic kidney-293 cells overexpressing different TRP channels. The data show that the toxicity of mesoporous silica nanoparticles was influenced by expression of the TRPA1 and TRPM2 channels, whereas the toxicity of smaller nonporous silica nanoparticles was only affected by TRPM8. Additionally, TRPA1 and TRPM2 played a role in the cytotoxicity of cationic dendrimers, but not anionic dendrimers. TRPV4 did not seem to play a significant role in silica nanoparticle or PAMAM toxicity.