Curcumin and Graphene Oxide Incorporated into Alginate Hydrogels as Versatile Devices for the Local Treatment of Squamous Cell Carcinoma.

Michael Mertig,Valerio Voliani,Giuseppe Cirillo,Orazio Vittorio,Patrizia Sarogni,Silke Hampel,Bernd Büchner,Manuela Curcio,Lorenzo Francesco Madeo,Tyler Shai-Hee

doi:10.3390/ma15051648

Abstract

With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100–170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized.

Highlights

The interest in graphene and the materials derived from it for biomedical applications has grown tremendously in recent years [1,2,3,4]
Among the plethora of naturally occurring molecules used in biomedicine, our interest was drawn to curcumin (CUR), a diferuloylmethane constituent of the yellow pigments isolated from Curcuma longa, which is well known for its antioxidant, radical-scavenging, antimicrobial, and anti-inflammatory properties [18,19]
The achievement of physical crosslinking presents a significant advantage over chemical crosslinking strategies, since the latter often require the use of crosslinking agents, solvents, and other chemicals, which need to be removed at the end of the process [49,50]

Summary

Introduction

The interest in graphene and the materials derived from it for biomedical applications has grown tremendously in recent years [1,2,3,4]. Among the plethora of naturally occurring molecules used in biomedicine, our interest was drawn to curcumin (CUR), a diferuloylmethane constituent of the yellow pigments isolated from Curcuma longa, which is well known for its antioxidant, radical-scavenging, antimicrobial, and anti-inflammatory properties [18,19] It has shown potent antiproliferative effects against several cancers due to its ability to interfere with different cellular pathways involved in carcinogenesis [20,21]. CUR has been tested both in vitro and in vivo against a large number of tumors [22,23,24], sparking its interest as a potential skin cancer treatment [25,26], whereby several studies have supported CUR as a potential candidate for the treatment of squamous cell carcinoma (SCC) [27,28,29]

Methods

Results

Conclusion