Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy

Deniz A. Boeluekbas, Stefan Datz, Charlotte Meyer-Schwickerath, Carmelo Morrone, Ali Doryab, Dorothee Goessl, Malamati Vreka, Lin Yang, Christian Argyo, Sabine H. van Rijt, Michael Lindner, Oliver Eickelberg, Tobias Stoeger, Otmar Schmid, Sandra Lindsted, Georgios T. Stathopoulos, Thomas Bein, Darcy E. Wagner*, Silke Meiners*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

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 & x2500;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.

Original languageEnglish
Article number2000017
Number of pages14
JournalAdvanced Therapeutics
Volume3
Issue number7
DOIs
Publication statusPublished - Jul 2020
Externally publishedYes

Keywords

  • biological barriers
  • lung cancer
  • nanoparticles
  • organ-restricted vascular delivery
  • solid tumors
  • NONSMALL CELL LUNG
  • GROWTH-FACTOR RECEPTOR
  • MESOPOROUS SILICA NANOPARTICLES
  • K-RAS
  • NANOMEDICINE
  • MACROPHAGE
  • MANAGEMENT
  • CLEARANCE
  • MECHANISM
  • PEPTIDE

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