The field of nanomedicine has received much attention for its potential to allow for targeted identification and treatment of tumors, while sparing healthy tissue. This promise has yet to be clinically realized; instead nanomedicine has translated into clinical benefit via formulations that improve the pharmacokinetics and toxicity profiles of toxic chemotherapeutic agents. It is well recognized that clearance by the mononuclear phagocytic system (MPS), particularly the liver, is the primary challenge to achieving tumor targeted delivery. However, it remains unclear exactly what drives liver accumulation. Kuppfer cells have been repeatedly identified as liver cells that uptake nanoparticles and there has been work focused on developing nanoparticles that avoid macrophage uptake in order to thus avoid liver clearance.<br/>We have recently shown that small molecule coatings on metallic nanoparticles can markedly reduce in vitro cell uptake for very sparsely PEGylated nanoparticles. Similar results were obtained in media with and without proteins, suggesting that protein opsonization is not the primary driver of this phenomenon. However, in vivo, these materials robustly accumulate in the liver (and other MPS organs) highlighting an in vitro/in vivo disconnect common to many nanoparticles. We have now conducted detailed studies of liver uptake of these and related materials and present a model to reconcile the results.

Investigating the <i>in vitro/in vivo</i> disconnect using gold nanoparticles

256th National Meeting (2018)

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Investigating the in vitro/in vivo disconnect using gold nanoparticles