Enhanced Drug Delivery into Cell Cytosol via Glycoprotein H-Derived Peptide Conjugated Nanoemulsions

5 years ago

Enhanced Drug Delivery into Cell Cytosol via Glycoprotein H-Derived Peptide Conjugated Nanoemulsions

Nicola Maurea, Chiara Di Cicco, Concetta Di Natale, Maria De Gregorio, Pasqualina Liana Scognamiglio, Claudio Arra, Paolo A. Netti, Teresa Fotticchia, Vincenzo Quagliariello, Luca Raiola, Chiara Attanasio, Rosario V. Iaffaioli, Antonio Barbieri, Vincenzo Calcagno, Daniela Guarnieri, Raffaele Vecchione

The key role of nanocarriers in improving the pharmacological properties of commonly used drugs is recognized worldwide. It is also known that in the development of new effective nanocarriers the use of targeting moieties integrated on their surface is essential. Herein, we propose a nanocarrier based on an oil in water nanoemulsion coated with a membranotropic peptide derived from the glycoprotein H of Herpes simplex virus 1, known as gH625, in order to reduce endolysosomal accumulation and to enhance cytosolic localization. In addition, we show an enhanced anti-inflammatory activity of curcumin, a bioactive compound isolated from the Curcuma longa plant, when loaded into our engineered nanocarriers. This effect is a consequence of a higher uptake combined with a high curcumin preservation exerted by the active nanocapsules compared to control ones. When loaded into our nanocapsules, indeed, curcumin molecules are directly internalized into the cytosol rather than into lysosomes. Further, in order to extend the in vitro experimental setting with a more complex model and to explore the possibility to use our nanocarriers for further biological applications, we tested their performance in a 3D sprouting angiogenesis model. Finally, we show promising preliminary in vivo results by assessing the anti-inflammatory properties of the proposed nanocarrier.

Publisher URL: http://dx.doi.org/10.1021/acsnano.7b03058

DOI: 10.1021/acsnano.7b03058