In Autumn 2020, DOAJ will be relaunching with a new website with updated functionality, improved search, and a simplified application form. More information is available on our blog. Our API is also changing.

Hide this message

Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery

Scientific Reports. 2019;9(1):1-14 DOI 10.1038/s41598-019-50538-w

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Sijumon Kunjachan (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Shady Kotb (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Robert Pola (Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic)

Michal Pechar (Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic)

Rajiv Kumar (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Bijay Singh (Nanomedicine Science and Technology Center and Department of Physics, Northeastern University)

Felix Gremse (Experimental Molecular Imaging, University Hospital and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University)

Reza Taleeli (Division of Medical Physics & Engineering, University of Texas Southwestern Medical Center)

Florian Trichard (Institut Lumière Matière, UMR 5306, Université Claude Bernard Lyon 1, CNRS)

Vincent Motto-Ros (Institut Lumière Matière, UMR 5306, Université Claude Bernard Lyon 1, CNRS)

Lucie Sancey (Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS UMR 5309 Joint Research Center)

Alexandre Detappe (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Sayeda Yasmin-Karim (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Andrea Protti (Lurie Family Imaging Center, Department of Radiology, Dana-Farber Cancer Institute and Harvard Medical School)

Ilanchezhian Shanmugam (Nanomedicine Science and Technology Center and Department of Physics, Northeastern University)

Thomas Ireland (LA-ICP-MS and ICP-ES Laboratories, Department of Earth and Environmental Sciences, Boston University)

Tomas Etrych (Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic)

Srinivas Sridhar (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Olivier Tillement (Institut Lumière Matière, UMR 5306, Université Claude Bernard Lyon 1, CNRS)

Mike Makrigiorgos (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

Ross I. Berbeco (Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

Abstract 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.