Graphene oxide containing hyaluronic acid based nanogels for the potential treatment of colorectal cancer

Abstract

Here, we reported the production of graphene oxide (GO) containing nanogels produced by a top-down procedure employing as a starting biomaterial an amino derivative of hyaluronic acid named HA-EDA. This derivative was reacted, in the presence of single layer GO, with α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-((2-aminoethyl)-carbamate)-divinyl sulfone (PHEA-DVS) employed as a macromolecular crosslinking agent. The so obtained hydrogel was homogenized by ultra-turrax and high pressure homogenizer and nanogels with Z-average of 390 nm and PDI of 0.22 were obtained. These nanogels were employed to incorporate Irinotecan (IT), an antitumor drug used in the treatment of colorectal carcinoma. It was demonstrated that GO gives hyperthermic properties to the nanogels and that this effect influences the release of the antitumor drug. The presence of IT gives to the nanogel cytotoxic effect toward colon cancer cells similar to that of the free drug. It was demonstrated that there is an adjuvant effect between hyperthermia and cytotoxicity of IT that could potentially allow to employ safer amounts of the drug during the treatment. A three-dimensional system for the co-culture of both healthy and tumor cells it was employed to study the possibility to employ the nanogel dispersion for the thermoablation of solid tumors. Obtained results suggest a potential dual mode anticancer activity of the obtained nanosystems.