Ionizing radiation increases systemic nanoparticle tumor accumulation

Abstract

Nanoparticle-based therapies are currently being explored for both the imaging and treatment of primary and metastatic cancers. Effective nanoparticle cancer therapy requires significant accumulations of nanoparticles within the tumor environment. Various techniques have been used to improve tumor nanoparticle uptake and biodistribution. Most notable of these techniques are the use of tumor-specific-peptide-conjugated nanoparticles and chemical modification of the nanoparticles with immune-evading polymers. Another strategy for improving the tumor uptake of the nanoparticles is modification of the tumor microenvironment with a goal of enhancing the enhanced permeability and retention effect inherent to solid tumors. We demonstrate a two-fold increase in the tumor accumulation of systemically delivered iron oxide nanoparticles following a single, 15 Gy radiation dose in a syngeneic mouse breast tumor model. This increase in nanoparticle tumor accumulation correlates with a radiation-induced decrease in tumor interstitial pressure and a subsequent increase in vascular permeability. Keywords ionizing radiation; nanoparticle; tumor; biodistribution; interstitial pressure BackgroundA variety of hyperthermia-based techniques[1], including intratumoral magnetic nanoparticle (mNP) hyperthermia [2], have been used to treat tumors. The difference in mNP hyperthermia, as compared to conventional hyperthermia, is the ability tofocally heat according to mNP uptake and biodistribution in both primary and metastatic tumors. One of the most significant challenges is delivering an effective concentration ofnanoparticles to tumor cells. Investigators have relied on increasing nanoparticle circulation time through evasion of the reticuloendothelial system (RES) [2] by modifying nanoparticle surface © 2012 Elsevier Inc. All rights reserved. * author(s) to whom correspondence should be addressed: andrew.j.giustini.th@dartmouth.edu.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Financial and competing interests disclosure: The authors report no conflicts of interest. NIH Public Access Materials Methods Cell CultureMTG-B mouse mammary adenocarcinoma cells were cultured in 150 cm 2 cell culture flasks (Corning Inc., Lowell, MA) in Alpha MEM medium (10% fetal bovine serum, 1% penicillin-streptomycin, 1% L-glutamine; all from Thermo Fisher Scientific Inc., Waltham, MA., USA). Cells were then trypsinized (0.25% trypsin in EDTA, Mediatech, Inc., Manassas, Va) and resuspended in serum-free Alpha MEM at 10 7 cells/ml. Murine tumor modelOne hundred μL (10 6 cells) was implanted bilaterally in ...

Spatial and temporal mapping of heterogeneity in liposome uptake and microvascular distribution in an orthotopic tumor xenograft model

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Neoantigen activation, Protein Translocation and Targeted Drug Delivery in Combination With Radiotherapy

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