Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.

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Nanocarriers show incredible potential in theranostic applications as they offer diagnostic capabilities along with the ability to encapsulate and protect drugs from degradation, be functionalized with targeting moieties and be designed with controlled release mechanisms. Most clinically approved nanocarrier drugs are liposomal formulations. As such, considerable research has been directed towards designing liposomal carriers that can release their payloads via exogenous or endogenous triggers. For triggered release to effectively increase drug bioavailability, nanocarriers must first accumulate at the tumor site via the enhanced retention and permeability effect. It has been demonstrated in the chicken embryo chorioallantoic membrane and murine xenografted models that nanoparticle surface charge and geometry, with respect to vascular endothelium fenestration size, drive this accumulation in angiogenic tissue.

Recently, nanoparticles (NPs) have been established as ideal drug delivery vehicles for treating cancer. This is due to the enhanced permeability and retention (EPR) effect that is a direct result of the angiogenic nature of the tumor tissue and its ability to sequester chemotherapeutics from healthy tissues. Ideal drug delivery nanocarriers will exploit the EPR effect, accumulate in the tumorous tissue, and be able to release the drugs at a high concentration where needed, thereby reducing undesirable side effects. In order to determine ideal NP qualities that enable drugs to be delivered in such a manner, extensive testing in biological systems is required. However, it is impractical to study new potential nanocarriers in humans or in mammalian models due to the potential adverse consequences, low throughput, and high cost. Simpler models would allow for higher throughput screening of nanocarrier vehicles. This review outlines the most recent advances in alternative model assays and their significance in testing NPs en route to the clinic. In decreasing complexity, we examine zebrafish embryos, the chorioallantoic membrane of the chicken embryo, multicell static and flow-based assays, and single cell assays for efficacy, accuracy and utility as predictors for human therapeutic outcomes.

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