Informed by our previous work, we used a small EV carrying GPI-anchored PH20 hyaluronidase (Exo-PH20) that could deeply penetrate into tumour foci via HA degradation.
To minimize the premature release, hyaluronic acid (HA) was further coating on the outer surface of pSiO<sub>2</sub>, which would be degraded by over-expressed hyaluronidase (Hyal-1) in the tumor microenvironment.
Expression of Hyal 3 and Hyal 2 mRNA were >1000-fold and >30-fold greater respectively than that of Hyal 1 mRNA, the major Hyal expressed in other cancers.No Hyal type varied with tumor grade.
In ex vivo xenograft tumor cell lines, however, hyal-1 or hyal-2 mRNA levels were frequently elevated, whereas LUCA3 was only infrequently elevated and PH20 not at all.