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 journalArticlepeer-review

45 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

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

ASJC Scopus subject areas

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

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