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Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy

Bölükbas, Deniz LU ; Datz, Stefan ; Meyer-Schwickerath, Charlotte ; Morrone, Carmela ; Doryab, Ali ; Gössl, Dorothee ; Vreka, Malamati ; Yang, Lin ; Argyo, Christian and van Rijt, Sabine , et al. (2020) In Advanced Therapeutics 3(7).
Abstract

Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic... (More)

Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ-restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras-mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell-specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ-restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biological barriers, lung cancer, nanoparticles, organ-restricted vascular delivery, solid tumors
in
Advanced Therapeutics
volume
3
issue
7
article number
2000017
publisher
Wiley-Blackwell
external identifiers
  • scopus:85103198373
  • scopus:85103198373
  • pmid:33884290
ISSN
2366-3987
DOI
10.1002/adtp.202000017
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
e9af8f9d-b744-41f4-90ea-7a2ac2982b9e
date added to LUP
2020-05-14 20:14:13
date last changed
2024-03-04 18:50:32
@article{e9af8f9d-b744-41f4-90ea-7a2ac2982b9e,
  abstract     = {{<p>Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ-restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras-mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell-specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ-restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.</p>}},
  author       = {{Bölükbas, Deniz and Datz, Stefan and Meyer-Schwickerath, Charlotte and Morrone, Carmela and Doryab, Ali and Gössl, Dorothee and Vreka, Malamati and Yang, Lin and Argyo, Christian and van Rijt, Sabine and Lindner, Michael and Eickelberg, Oliver and Stoeger, Tobias and Schmid, Otmar and Lindstedt, Sandra and Stathopoulos, Georgios T and Bein, Thomas and Wagner, Darcy E. and Meiners, Silke}},
  issn         = {{2366-3987}},
  keywords     = {{biological barriers; lung cancer; nanoparticles; organ-restricted vascular delivery; solid tumors}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Advanced Therapeutics}},
  title        = {{Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy}},
  url          = {{http://dx.doi.org/10.1002/adtp.202000017}},
  doi          = {{10.1002/adtp.202000017}},
  volume       = {{3}},
  year         = {{2020}},
}