Exosome as a Vehicle for Delivery of Membrane Protein Therapeutics, PH20, for Enhanced Tumor Penetration and Antitumor Efficacy

Yeonsun Hong, Gi Hoon Nam, Eunee Koh, Sangmin Jeon, Gi Beom Kim, Cherlhyun Jeong, Dong-Hwee Kim, Yoosoo Yang, In-San Kim

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

As biochemical and functional studies of membrane protein remain a challenge, there is growing interest in the application of nanotechnology to solve the difficulties of developing membrane protein therapeutics. Exosome, composed of lipid bilayer enclosed nanosized extracellular vesicles, is a successful platform for providing a native membrane composition. This study reports an enzymatic exosome, which harbors native PH20 hyaluronidase (Exo-PH20), which is able to penetrate deeply into tumor foci via hyaluronan degradation, allowing tumor growth inhibition and increased T cell infiltration into the tumor. This exosome-based strategy is developed to overcome the immunosuppressive and anticancer therapy-resistant tumor microenvironment, which is characterized by an overly accumulated extracellular matrix. Notably, this engineered exosome with the native glycosylphosphatidylinositol-anchored form of hyaluronidase has a higher enzymatic activity than a truncated form of the recombinant protein. In addition, the exosome-mediated codelivery of PH20 hyaluronidase and a chemotherapeutic (doxorubicin) efficiently inhibits tumor growth. This exosome is designed to degrade hyaluronan, thereby augmenting nanoparticle penetration and drug diffusion. The results thus show that this is a promising exosome-based platform that harbors not only a membrane-associated enzyme with high activity but also therapeutic payloads.

Original languageEnglish
Article number1703074
JournalAdvanced Functional Materials
Volume28
Issue number5
DOIs
Publication statusPublished - 2018 Jan 31

Keywords

  • cancer therapy
  • doxorubicin
  • exosomes
  • GPI-anchored proteins
  • PH20

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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