Proceedings of the 5 th World Congress on Recent Advances in Nanotechnology (RAN'20) Lisbon, Portugal Virtual Conference– October 2020 Paper No. NDDTE 122 DOI: 10.11159/nddte20.122 NDDTE 122-1 Fullerene (C60) Evaluation for Photodynamic Therapy Seyed M. Heidari 1 , Mohadese Golsorkhi 2 1 Michigan State University, College of Engineering 1449 Engineering Research Ct., A119, East Lansing, 48823 MI, USA Heidari1@msu.edu; golsorkhi.m93@gmail.com 2 Mashhad University of Medical Sciences, Department of Medicine Mashhad, Iran Extended Abstract Cancer is the second leading cause of death globally [1]. World Health Organization reported 9.6 million cancer- related deaths only in 2018 [2]. Although there have been advances in cancer therapy, the development of anti-tumor strategies faces many limitations. The main cancer-treating methods—chemotherapy and radiotherapy—compromise the host’s immune system and have many other systemic side effects [3]. Recently, photodynamic therapy (PDT) has attracted attention in cancer treatment due to its non-invasive and highly selective properties [4], [5]. The idea behind PDT is using a photosensitizer with varying affinity to malignant and normal cells resulting in different concentrations of the agent in cells. Subsequently, an appropriate wavelength light irradiation on target cells produces reactive oxygen species (ROS) due to the photosensitizer leading to cellular damage [6]. Various photosensitizers are used in PDT. Most of them are porphyrin-based dyes with low quantum yield, little tumor targetability, high-power laser light exposure requirement, and general side effects on healthy tissue [7]. Meantime, fullerene (C60), a new class of nanocarbon molecules with 60 carbon atoms in a closed cage structure, has been introduced as an efficient and non-toxic photosensitizer [8]. Due to the unique photoproduction abilities of C60 fullerenes, they can generate singlet oxygen and other ROS (O2 - , H2O2, HO • ) under the influence of visible light irradiation [9]. Besides, C60 accumulates in malignant cells selectively and inhibits key enzyme systems competitively [10]. This reduces systematic side effects in the body compared to chemotherapy and other photodynamic agents [11]. However, C60 fullerenes have some limitations. For example, C60 is insoluble in polar solvents, which limits its application in biological studies. Therefore, C60 bioavailability must be enhanced by adding water-soluble functional groups [12], [13]. This study reviewed related studies since 1996 about different hydrophilic agents, such as polyethylene glycol (PEG), nano-silica, carboxylic acids, human serum albumin, glycogen, polyethylene oxide, glycol chitosan, and viral nanoparticles, added to C60 to increase water solubility. We analyzed the reported results for C60 hydrophilic agent combinations that were examined in vivo or in vitro under a specific wavelength light irradiation. As a result of the cytotoxicity ability of the C60-agent combination, cell viability was used as one of our main indicators to compare PDT efficacy of various C60-agent combinations. It was found that C60 conjunctions could increase the functionality of fullerenes in treating different cancer cells. PDT efficacy is not all, and we need to focus on the side effects as well. The major challenge in cancer treatment strategies is to limit systemic side effects. For this purpose, drug delivery systems (DDSs) have been designed to destroy target cells selectively. They also control and prolong drug release by protecting the drug from degrading enzymes [14]. A DDS consists of three main parts: 1) an addressing unit to recognize selected targets, 2) a multiplying unit to increase the number of drug molecules, and 3) an active biological unit. In the second part of our review article, we explained different substances like liposome, graphene, transferrin, pullulan, etc. as drug delivery agents added to C60 to maximize its therapeutic effects and minimize its side effects spontaneously [15]. In conclusion, drug delivery systems using C60 showed a strong anti-tumor efficacy compared to free drugs under irradiation. In the last part of this study, we investigated the application of porphyrin-C60 and chlorine-C60 dyads in PDT to enhance ROS production in PDT. Recently, porphyrins, phthalocyanines, and chlorines have been recommended as therapeutic properties in PDT. Based on recent studies, we evaluated the functionality of porphyrin-C60 and chlorine-C60 dyads for producing long-lived radical ion pairs under irradiation, which makes these combinations very efficient sensitizers for PDT [16]. Finally, the combination could reduce cell viability significantly under light irradiation.