Organ-restricted vascular delivery of nanoparticles for lung cancer therapy.

Autor: Bölükbas DA; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany; Lung Bioengineering and Regeneration, Dept of Experimental Medical Sciences, Stem Cell Centre, Wallenberg Center for Molecular Medicine, Lund University Cancer Centre (LUCC), Lund University, 22362 Lund, Sweden., Datz S; Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU) 81377 Munich, Germany., Meyer-Schwickerath C; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Morrone C; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Doryab A; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Gößl D; Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU) 81377 Munich, Germany., Vreka M; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany; Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, 26504 Patras, Greece., Yang L; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Argyo C; Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU) 81377 Munich, Germany., van Rijt SH; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Lindner M; Center of Thoracic Surgery Munich, Asklepios Clinic Munich-Gauting, and Asklepios Biobank for Diseases of the Lung, Comprehensive Pneumology Center (CPC), Ludwig-Maximilians University and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), 82131 Gauting, Germany., Eickelberg O; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Stoeger T; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Schmid O; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany., Lindstedt S; Dept of Cardiothoracic Surgery, Heart and Lung Transplantation, Lund University Hospital 22242 Lund, Sweden., Stathopoulos GT; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany; Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, 26504 Patras, Greece., Bein T; Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU) 81377 Munich, Germany., Wagner DE; Lung Bioengineering and Regeneration, Dept of Experimental Medical Sciences, Stem Cell Centre, Wallenberg Center for Molecular Medicine, Lund University Cancer Centre (LUCC), Lund University, 22362 Lund, Sweden., Meiners S; Comprehensive Pneumology Center (CPC), University Hospital Ludwig-Maximilians University, and Helmholtz Zentrum München, Munich, Germany. Member of the German Center for Lung Research (DZL), 81377 Munich, Germany.
Jazyk: angličtina
Zdroj: Advanced therapeutics [Adv Ther (Weinh)] 2020 May 13; Vol. 3 (7). Date of Electronic Publication: 2020 May 13 (Print Publication: 2020).
DOI: 10.1002/adtp.202000017
Abstrakt: 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 EGFR and CCR2 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.
Databáze: MEDLINE
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