Cancer nanomedicinal and bioimaging strategies in the literature often rely on exploiting the enhanced permeability and retention (EPR) effect of the tumor vasculature to assess the tumor cells. However, there are several issues if there is the sole dependence on the EPR effect to access the tumor. Since the EPR effect of leaky cancer vasculature is derived from the tumor, it is unpredictable and makes sub-tumor region targeting, a hit-and-miss endeavor. Moreover, the EPR effect is initiated by a more mature tumor which ironically carries more drug resistance. This limits any EPR dependent nanomedicine to only begin to access a more difficult to kill tumor instead of accessing and kiling a less mature and more vulnerable tumor. We described several non-EPR dependent nanobiotechnological strategies with the overall future goal of accessing an immature tumor through the vasculature. We showed that we could almost induce permeability at will through tinkering with nanoparticles induced oxidative stress; through controlling the density and size parameters of nanomaterials to induce endothelial cells leakiness (NanoEL). These studies represent our current paradigm shifts towards a more proactive approach towards accessing the tumors (especially immature tumors) from the vasculature.

Developing endothelial targeted nanotechnologies to wean cancer nanomedicine and bioimaging nanotechnology off the EPR effect

254th National Meeting (2017)

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