Therapeutic Remodeling of the Tumor Microenvironment Enhances Nanoparticle Delivery

Yuanxin Chen, Xiujie Liu, Hengfeng Yuan, Zhaogang Yang, Christina A. von Roemeling, Yaqing Qie, Hai Zhao, Yifan Wang, Wen Jiang, Y S Betty Kim

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability. Furthermore, the tumor extracellular matrix (ECM), unlike that of the normal tissue parenchyma, is densely packed with collagen. These pathophysiological properties greatly impede intratumoral delivery of nanomaterials. By using an antivascular endothelial growth factor receptor antibody, DC101, and an antitransforming growth factor β1 (TGF-β1) antibody, normalization of the tumor vasculature and ECM is achieved, respectively, in a syngeneic murine glioma model. This normalization effect results in a more organized vascular network, improves tissue perfusion, and reduces collagen density, all of which contribute to enhanced nanoparticle delivery and distribution within tumors. These findings suggest that combined vascular and ECM normalization strategies can be used to remodel the tumor microenvironment and improve nanomedicine delivery into solid tumors, which has significant implications for developing more effective combinational therapeutic strategies using cancer nanomedicine.

Original languageEnglish (US)
Article number1802070
JournalAdvanced Science
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • DC101
  • extracellular matrix
  • nanomedicine delivery
  • normalization
  • TGFβ
  • tumor vasculature

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Chen, Y., Liu, X., Yuan, H., Yang, Z., von Roemeling, C. A., Qie, Y., Zhao, H., Wang, Y., Jiang, W., & Kim, Y. S. B. (Accepted/In press). Therapeutic Remodeling of the Tumor Microenvironment Enhances Nanoparticle Delivery. Advanced Science, [1802070]. https://doi.org/10.1002/advs.201802070