Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy
(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.
(Less)
- author
- organization
-
- LUCC: Lund University Cancer Centre
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Lung Bioengineering and Regeneration (research group)
- Clinical and experimental lung transplantation (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- NPWT technology (research group)
- DCD transplantation of lungs (research group)
- Thoracic Surgery
- publishing date
- 2020-07-01
- 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}}, }