Hyaluronidase and a low density second PEG layer on the surface of therapeutic-encapsulated nanoparticles to enhance nanoparticle diffusion and circulation

Abstract

A delivery system comprising an organic nanoparticle, a hyaluronidase anchored or conjugated to the organic nanoparticle. The organic nanoparticle may be selected from a polymer-based nanoparticle, a lipid-based nanoparticle and nanoparticle formed by lipid-like molecules. In some embodiments, the hyaluronidase is covalently bound to a linker or spacer which, in turn, is anchored or covalently bound to the organic nanoparticle. The delivery system may also comprise an active pharmaceutical agent, a diagnostic agent, and/or a cellular membrane. The organic nanoparticle may further have a low density poly(ethylene glycol) layer on the surface. Methods for using the delivery system including for treating or diagnosing a disease are also provided. The organic nanoparticle provides enhanced diffusion/penetration through the extracellular matrix found in tumors, as well as increased circulation time in a human or animal body.

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