Exfoliated graphene nanosheets: pH-sensitive drug carrier and anti-cancer activity.
A straightforward and facile method for the exfoliation of graphene sheets using poly(vinylpyrrolidone) nanoparticles of an average size of 42nm was developed and their dual role as pH-sensitive drug carrier and anti-cancer agent was evaluated. The cytotoxic impact of the exfoliated nanosheets (GRP-PVP-NP) was examined on various cells (HCT-116, HeLa, SCC-9, NIH-3T3 and HEK-293cells) by a series of assays. Their cytotoxic nature was attributed to affecting the mitochondrial enzyme activity, proliferation capability, and the formation of tight junctions in cancer cells. The endocytosis was found to be internalization mechanism for the cellular uptake of nanosheets. The generation of reactive oxygen species and elicitation of caspase-3 activity which was undoubtedly associated with triggering of oxidative stress speculated to be the dominant cause of the cytotoxic pattern of nanosheets against cancer cells. Additionally, the results also showed the role of the nanosheets as a pH-sensitive drug carrier through drug loading by supramolecular interaction. The efficient release of doxorubicin was seen at low pH and in an environment with a low oxygen concentration, thus under conditions mimicking the typical tumor microenvironment. Therefore, these findings provide the first evidence for a dual function of exfoliated graphene sheets and also elucidate the cytotoxic mechanism responsible for the cancer cell death.
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 500712, South Korea.
Nisha
N
Tyagi
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 500712, South Korea; Fire Protection Laboratory, Chemistry Division, National Institute of Standards, 136, Giza 12211, Egypt.
Nour F
NF
Attia
School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 500712, South Korea; Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology (GIST), Gwangju 500712, South Korea. Electronic address: keg@gist.ac.kr.
Kurt E
KE
Geckeler
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005456:Fluorescent Dyes / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods; D018384:Oxidative Stress; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D006108:Graphite; D004317:Doxorubicin; D011205:Povidone
Cancer cells; Cytotoxicity; Drug carrier; Graphene; Nanosheets