Xin Zeng1,2, Yi Yuan3, Ting Wang4, Han Wang3, Xianyun Hu5, Ziyi Fu2, Gen Zhang6, Bin Liu7, Guangming Lu8. 1. Department of Medical Imaging, Jingling Hospital, School of Medicine, Nanjing Universtiy, Nanjing, 210002, China. 2. Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China. 3. Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China. 4. Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. 5. Department of Biochemistry, Qiannan Medical College for Nationalities, Duyun, 558000, China. 6. Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. zhanggen123@126.com. 7. Department of Biomedical Engineering, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China. sslb_112@hotmail.com. 8. Department of Medical Imaging, Jingling Hospital, School of Medicine, Nanjing Universtiy, Nanjing, 210002, China. cjr.luguangming@vip.163.com.
Abstract
BACKGROUND: Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. RESULTS: In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. CONCLUSION: In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.
BACKGROUND: Currently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging. RESULTS: In the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. ThemiR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging. CONCLUSION: In conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.
Authors: John F P Bridges; Liming Dong; Gisselle Gallego; Barri M Blauvelt; Susan M Joy; Timothy M Pawlik Journal: BMC Health Serv Res Date: 2012-10-30 Impact factor: 2.655