I am working with 50 nm titanium dioxide coated heavy-metal based nanoparticles. The size is 50 nm. 4 hours following IV administration of about 10 mg/kg (around 90-100ul depending on weight of mice that is around 20 mg), I observed black spots in the lung of mice. This was also seen in mice sacrificed 24 hours after injection. However in mice sacrificed 1 and 2 week after injection, these spots were not observed and the lungs looked normal. What could be the cause? How can this be avoided?
Nanoparticle formulations that are not stable in blood circulation can form agglomerates that have been reported to be able to occluce the pulomnary micro-vasculator. The black spots may be areas of occluded micro vasculator that is the result of nanoparticle agglomeration/adsorption of plasma proteins. The disappearance of the black spots after 1-2 weeks could be the clearance of the nanoparticles from the body. Do you have any data on the stability of your nanoparticles in biologically relevent conditions (incubation at 37 degrees and diluted with 10% fetal bovine serum in phosphate buffered saline or with mouse plasma)? What is the zeta potential of your nanoparticles? Nanoparticles with strongly positive zeta potentials have been reported for their rapid absorption of plasma proteins, and subsequent destablization. The addition of a surfactant coating (neutral - PEG, poloxomers or negative - polysorbant 80, polysorbant 20, etc) may be able to mitigate instability issues. Digestion of the pulmonary tissue with nitrite acid and analysis for titanium via Inductively coupled plasma atomic emission spec (ICP-AES; or ICP-OES / ICP-MS) would be able to provide you with a definite answer if the black spots are composed of your nanoparticles.
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