Graphene as cancer theranostic tool: progress and future challenges. Marco Orecchioni, Roberto Cabizza, Alberto Bianco, Lucia Gemma Delogu To cite this version: Marco Orecchioni, Roberto Cabizza, Alberto Bianco, Lucia Gemma Delogu. Graphene as cancer theranostic tool: progress and future challenges.. Theranostics, Ivyspring International Publisher, 2015, 5 (7), pp.710-723. 10.7150/thno.11387. hal-02558879 HAL Id: hal-02558879 https://hal.archives-ouvertes.fr/hal-02558879 Submitted on 29 Apr 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Theranostics 2015, Vol. 5, Issue 7 710 Ivyspring International Publisher Theranostics 2015; 5(7): 710-723. doi: 10.7150/thno.11387 Review Graphene as Cancer Theranostic Tool: Progress and Future Challenges Marco Orecchioni1, Roberto Cabizza1, Alberto Bianco2 and Lucia Gemma Delogu1 1. Department of Chemistry and Pharmacy, University of Sassari , via muroni 23 07100 Sassari, Italy 2. CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunologiepathologie et Chimie Thérapeutique, 15 rue René Des- cartes, 67000 Strasbourg, France Corresponding author: E-mail: [email protected] © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. Received: 2014.12.18; Accepted: 2015.02.04; Published: 2015.03.28 Abstract Nowadays cancer remains one of the main causes of death in the world. Current diagnostic techniques need to be improved to provide earlier diagnosis and treatment. Traditional therapy approaches to cancer are limited by lack of specificity and systemic toxicity. In this scenario na- nomaterials could be good allies to give more specific cancer treatment effectively reducing un- desired side effects and giving at the same time accurate diagnosis and successful therapy. In this context, thanks to its unique physical and chemical properties, graphene, graphene oxide (GO) and reduced graphene (rGO) have recently attracted tremendous interest in biomedicine including cancer therapy. Herein we analyzed all studies presented in literature related to cancer fight using graphene and graphene-based conjugates. In this context, we aimed at the full picture of the state of the art providing new inputs for future strategies in the cancer theranostic by using of graphene. We found an impressive increasing interest in the material for cancer therapy and/or diagnosis. The majority of the works (73%) have been carried out on drug and gene delivery applications, following by photothermal therapy (32%), imaging (31%) and photodynamic therapy (10%). A 27% of the studies focused on theranostic applications. Part of the works here discussed contribute to the growth of the theranostic field covering the use of imaging (i.e. ultrasonography, positron electron tomography, and fluorescent imaging) combined to one or more therapeutic modalities. We found that the use of graphene in cancer theranostics is still in an early but rapidly growing stage of investigation. Any technology based on nanomaterials can significantly enhance their possibility to became the real revolution in medicine if combines diagnosis and therapy at the same time. We performed a comprehensive summary of the latest progress of graphene cancer fight and highlighted the future challenges and the innovative possible theranostic applications. Key words: graphene, nanomedicine, carbon materials, cancer, tumor, theranostics, therapy. Introduction Despite the everyday progresses of medicine death worldwide with 8,2 million of death occurred in solutions for human health, today cancer is still one of 2012. It is estimated that by 2020, there will be be- the biggest challenges for humanity. Thanks to the tween 15 and 17 million new cases of cancer every advancements in prevention and in treatment, the year, 60% of which will be in developing countries [1]. survival rate has been improved in the last few years. In economical developed countries the burden of However, cancer remains one of the main causes of cancer is a result of population aging and growth as http://www.thno.org Theranostics 2015, Vol. 5, Issue 7 711 well as an increasing adoption of cancer-associated degradability in aqueous solutions. In addition, the lifestyle choices including smoking, physical inactiv- dimensions of the flakes of graphene could be re- ity, and ‘‘westernized’’ diets [2, 3]. Cancer, as defini- sponsible of different impacts on cell viability [19]. On tion, is the uncontrolled growth of cells that can occur the other hand, specific toxic effects of graphene on in any type of tissue and, at the late stage, these cells cancer cells could represent a positive point. Indeed, lose their adhesion capacities and migrate to healthy many reports have shown that this function of gra- tissues. Other than surgical treatment, the different phene could be useful in possible future therapeutic options are all based on a mechanical or pharmaco- applications [20, 21], for example as an inhibitor of logical killing action against cancer cells, possibly cancer cell metastasis [22]. Furthermore, different an- avoiding the side effect damages of healthy cells. ticancer biomolecules such as siRNA, DNA and other Nanotechnology is one of the best promises to drugs can be loaded onto the graphene surface for attack cancer cells more specifically, effectively and to gene silencing and transfection, drug delivery and reduce undesired side effects. In other terms, nano- many other cancer therapy applications [23]. technology can be used to transport drugs to a specific In this review we analyzed all studies presented site using specific keys such as antibodies. Moreover, in literature aiming to fight cancer using graphene in the context of developing innovative theranostics, and graphene-based conjugates. We found that the nanomaterials could be used for imaging as a diag- graphene strategies in fighting cancer can be summa- nostic tool and, at the same time, to stimulate and rized in 4 main groups: i) drug delivery, ii) photo- control the release of drugs in the cancer site. thermal therapy (PTT), iii) photodynamic therapy, In the recent years numerous nanomaterials (PDT) and iv) imaging. Furthermore, we evidenced have been explored for potential theranostic applica- the works where authors used diagnostic and differ- tions for cancer therapy thanks to their properties [4]. ent therapy strategies such as drug delivery into one Compared to traditional molecular contrast system promoting the use of graphene as a theranostic agents or drugs, nanomaterials can be engineered to tool. We also carefully evaluated the use and the im- improve and integrate multiple functions in a single pact of graphene by tumor type. Our purpose was to system also to give the control of drugs release, being broaden the knowledge of graphene as useful tech- of hope for the building of a next generation of anti- nology for the future of clinical cancer treatment and cancer tools [5]. diagnosis. In this work we point out what are the The relatively new nanomaterial, graphene, has lacking areas of graphene investigation from an on- attracted tremendous interest in the scientific com- cology point of view, underling what can be the most munity and in the public [6-9] being explored for promising approaches for the use of graphene-based many potential applications due to its unique physi- tools in the challenging field of cancer. co-chemical characteristics including electronic, opti- cal, thermal and mechanical properties [10-12]. The Studies selection criteria and overview precise structure of graphene has been the subject of To achieve our aim, we performed a “PubMed debate over the years since it varies greatly with the search” using the following keywords: graphene, preparation methods and extent of oxidation [13, 14]. graphene oxide, cancer therapy, drug delivery and Nevertheless, graphene can be rich in functional cancer, immunotherapy, imaging and cancer, cancer groups such as carboxylic and hydroxyl groups which diagnosis. The keyword exploration was done in facilitate its surface modifications. Very recently, several different combinations. High impact review graphene and graphene oxide (GO) have been inves- articles also served as additional tool. The list of re- tigated in a growing number of medical applications, ported studies includes all the retrieved publications such as drug delivery, diagnostics, tissue engineering from 2008 to November 2014. In table 1 we report a and gene transfection all with the final aim to use it as characterization of all the studies based on: type of a theranostic materials [15-18]. However, one of the application, type of cancer, species, model, type of main concerns of using graphene in nanomedicine is graphene in terms of functionalization, year of publi- its biocompatibility. Similarly to many other nano- cation and reference. materials, it is necessary to carefully address its bio- Table 1.