Multistage Nanocarrier Based on an Oil Core–Graphene Oxide Shell

Author:

Tufano Immacolata12,Vecchione Raffaele1ORCID,Panzetta Valeria123ORCID,Battista Edmondo14ORCID,Casale Costantino3,Imparato Giorgia1ORCID,Netti Paolo Antonio123

Affiliation:

1. Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, 80125 Naples, Italy

2. Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, 80138 Naples, Italy

3. Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, 80138 Naples, Italy

4. Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy

Abstract

Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier.

Publisher

MDPI AG

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