Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.
Fiche publication
Date publication
novembre 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DETAPPE Alexandre
Tous les auteurs :
Kunjachan S, Kotb S, Pola R, Pechar M, Kumar R, Singh B, Gremse F, Taleeli R, Trichard F, Motto-Ros V, Sancey L, Detappe A, Yasmin-Karim S, Protti A, Shanmugam I, Ireland T, Etrych T, Sridhar S, Tillement O, Makrigiorgos M, Berbeco RI
Lien Pubmed
Résumé
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 K (permeability), K (flux rate), and V (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.
Référence
Sci Rep. 2019 Nov 1;9(1):15844