Effective drug delivery is restricted by pathophysiological barriers in solid
tumors. In human pancreatic
adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the
tumor vascular barrier in a human
pancreatic cancer model. Clinical radiation activates the
tumor endothelial-targeted
gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these
tumor neovessels lead to distinct changes in
tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive
gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared
dye, demonstrate more than two-fold increase in nanodrug delivery, post
tumor vascular modulation. Functional changes in altered
tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted
therapy effectively invades the
tumor vascular barrier and improve nanodrug delivery in a human pancreatic
tumor model and it may also be applied to other nonresectable, intransigent
tumors that barely respond to standard
drug therapies.