Hong, Yeonsun Nam, Gi-Hoon Koh, Eunee Jeon, Sangmin Kim, Gi Beom Jeong, Cherlhyun Kim, Dong-Hwee Yang, Yoosoo Kim, In-San 2024-01-19T23:32:50Z 2024-01-19T23:32:50Z 2021-09-03 2018-01-31 1616-301X https://pubs.kist.re.kr/handle/201004/121791 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. English WILEY-V C H VERLAG GMBH CANCER-THERAPY EXTRACELLULAR VESICLES HYALURONAN SPERM MICROENVIRONMENT PH-20 NANOPARTICLES NANOMEDICINE PROGRESSION BIOGENESIS Exosome as a Vehicle for Delivery of Membrane Protein Therapeutics, PH20, for Enhanced Tumor Penetration and Antitumor Efficacy Article 10.1002/adfm.201703074 1 ADVANCED FUNCTIONAL MATERIALS, v.28, no.5 ADVANCED FUNCTIONAL MATERIALS 28 5 scie scopus 000423512300024 2-s2.0-85041021263 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Physics, Applied Physics, Condensed Matter Chemistry Science & Technology - Other Topics Materials Science Physics Article CANCER-THERAPY EXTRACELLULAR VESICLES HYALURONAN SPERM MICROENVIRONMENT PH-20 NANOPARTICLES NANOMEDICINE PROGRESSION BIOGENESIS cancer therapy doxorubicin exosomes GPI-anchored proteins PH20