Graphene is a widely studied and used nano material for its peculiar properties. In particular, graphene oxide (GO) has been used in medicine because of its low toxicity. One interesting and yet unknown application comes from the possibility to use GO to deliver molecules into the cells. In fact GO can be functionalized by using its natural COOH groups that allow binding of biomolecules.
In this context, our project aims to use a new technology for obtaining metal free GO that can be used to deliver more effectively exogenous molecules to tumor cells to interfere with vital functions.
Initially we will determine the intracellular accumulation of fluorescent GO to individuate the localization and the effect in term of cell death and transformation.
Next, we will use an GO-anti HMGB1 to deliver an antibody to tumor cells with the aim to modify their vitality, migration and invasion. In particular, we will study induction of apoptosis, autophagy and stemness in cells treated with GO-anti HMGB1.
In conclusion our study will give the possibility to demonstrate that functionalized GO can be used to increase the efficacy of anti-tumor strategies by delivering biomolecules to tumor cells.
Nanoparticles are increasingly used in the industrial and biomedical field because of their chemical and physical properties that allow them to readily penetrate into tumor cells. Interestingly, some nanoparticles such as graphene oxide (GO) nanoparticles do not affect or have minimal effects on mammalian cells. Moreover, graphene unique atomic structure allows functionalization and, in particular, GO can be functionalized with carboxylic groups (C=(O)OH) (1). Functionalized GO is suitable to bind various biological active molecules, to assemble new tools for drug delivery into cells.
In such a scientific context, our project aims to answer to two important questions:
1) does functionalized and metal-free GO possess a low toxicity and an high intracellular accumulation? In this case we will use FITC-GO to follow its accumulation inside tumor cells.
2) does functionalized GO bound to anti-HMGB1 antibody (GO-anti HMGB1) modify cellular vitality and/or behavior? In this case, since HMGB1 is overexpressed in tumor cells and is involved in cell motility, we will measure cell vitality and migration/invasion characteristics as well as modulation of molecular pathways such as apoptosis, autophagy and stemness.
In conclusion, our work aims to make a step towards the safe use of nanoparticles to deliver molecules (in this case an antibody) to tumor cells.
(1) Valentini F, et al. Int J Mol Sci. 2018;19(5).