Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability toestablish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled,mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging andmathematical modeling approach to understand the combined effects of MSN size, surfacechemistry and routes of administration on biodistribution and clearance kinetics in healthyrats. We show that increased particle size from ~32- to ~142-nm results in a monotonicdecrease in systemic bioavailability, irrespective of route of administration, with correspondingaccumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI)have reduced circulation, compared to MSNs of identical size and charge but with shieldedamines (QA), due to rapid sequestration into liver and spleen. However, QA show greatertotal excretion than PEI and their size-matched neutral counterparts (TMS). Overall, weprovide important predictive functional correlations to support the rational design ofnanomedicines.