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Weissleder, Ralph
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document
Predicting properties of nanoparticles for drug delivery and tissue targeting
Abstract
Nanoparticles are playing an increasingly important role in medicine, spawning the new field of nanomedicine. Amphiphilic lyotropic liquid crystalline self-assembled nanomaterials have great potential as delivery vehicles for drugs and imaging agents as they are biodegradable, adaptable to multiple drug sizes and types, have enhanced physical and chemical stability, and enhanced tissue and cellular uptake, properties valuable for new therapeutic or diagnostic applications. However, little is known about the effect of the incorporated drug on the structure of nanoparticles. Predicting these properties is widely considered intractable. We present computational models for three drug delivery carriers, loaded with 10 drugs at six concentrations and two temperatures. These models predicted nanophase behavior for 11 new drugs.1 Subsequent synchrotron small-angle X-ray scattering experiments validated the predictions. Hard nanoparticles, i.e. metallic, metal oxide nanoparticles and quantum dots, also play an important and complementary role to soft nanoparticles in medicine, particularly in tissue targeting and diagnostics. Computational models allow rapid prediction of tissue specificities, cellular uptake, and potential toxicities of new and modified nanomaterials, and leverage sparse and expensive experimental data. We generated quantitative, predictive models of cellular uptake and apoptosis induced by nanoparticles for several cell types.2 Of the cell lines tested, only the p PaCa2 and HUVEC lines showed significant variation in uptake of surface modified nanoparticles and generated robust predictive computational models for uptake.1. Le, TC; Mulet, X; Burden, FR; Winkler, DA Mol. Pharmaceut. 2013 10, 1368 2. Epa, VC; Burden, FR; Tassa, C; Weissleder, R; Shaw, S; Winkler, DA. Nano Lett., 2012, 12, 5808.