Real - time monitoring of tumor response to photothermal / photodynamic therapy by functional magnetic resonance imaging

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1 Journal of Fuzhou University Natural Science Edition Vol 43 No 5 Oct 2015 DOI /issn T2 R445 2 A Real - time monitoring of tumor response to photothermal / photodynamic therapy by functional magnetic resonance imaging CAO Jianbo FU Guifeng ZHANG Fan LIU Gang Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen Fujian China Abstract This paper assess the long - term curative effect of tumor after different treatment strategies Compared with photodynamic therapy or photothermal therapy alone the combined therapy showed a significantly synergistic effect which was demonstrated by functional MRI The results provide a direct non - invasive method for in vivo monitoring of the treatment response to nanoparticle - mediated PTT which can be used to guide cancer therapy to improve potential clinical outcomes Keywords functional MRI photothermal therapy photodynamic therapy real - time monitoring 0 photothermal therapy PTT photodynamic therapy PDT DWI 8 - DWI e6 G0 - PEG - Ce gangliu cmitm@ xmu edu cn

2 5 723 PEG nano - graphene oxide ngo RGO e6 chlorin e6 Ce6 630 ~ 700nm e T1 MTT μl ~ h μg ml - 1 GO - PEG - Ce6 24 h 24 h 5 mg L - 1 MTT 20 μl 4 h 100 μl DMSO 10 min 490 nm OD = / 100% MTT 96 5 μmol Ce6 GO - PEG - Ce h nm 10 min 0 3 W cm nm 5 min 0 05 W cm W cm nm 10 min 0 05 W cm nm 5 min MTT 4 h 100 μl DMSO 10 min 490 nm OD Balb /C 16 ~ 18 g 4T μl 20 PBS GO - PEG - Ce μl PBS 24 h nm 10 min 1 W cm nm 5 min 0 2 W cm W cm nm 10 min 0 2 W cm nm 5 min 10% 4 μl g MRI MRI d 5 9 4T Bruker 94 /20 USR Germany 4 cm RF 1H 75 /40 Bruker Germany MRI 1 T2 TurboRARE TR /TE = /33 ms mm 1 0 mm field of view FOV = 40 mm 40 mm 2 SE - DWI B 800 s mm - 2 TR /TE = /27 ms mm 1 0 mm FOV = 40 mm 40 mm 1 5 4% hematoxylin - eosin staining platelet endothelial cell adhesion molecule - 1 PECAM - 1 / CD31 CD31 1 h Cy3 IgG immunoglobulin G http / /xbzrb fzu edu cn

3 a MTT GO - PEG - Ce μg ml h 80% 200 μg ml % 1 b GO - PEG - Ce6 4 h 40% 30% 20% 1 Fig 1 Cell toxicity tests and photothermal therapeutic effect a T2 2 b ADC ADC apparent diffusion coefficient ADC DWI ADC PBS MRI ADC 14 d 4 ~ 5 2 a ADC 7 d ADC GO - PEG - Ce6 24 h Fig 2 2 In vivo MRI representative T2WI ADC - map and MRI evaluating tumor response after PTT http / /xbzrb fzu edu cn

4 ~ 49 MRI ADC 3 d 14 d 3 d ADC a T2 relative tumor volume PBS 4 ~ 5 3 d 7 d 14 d 3 d 3 b ADC ADC 1 d 3 d ADC 3 d ADC ADC PBS ADC 2 4 Fig 3 3 Effect of different treatment on the tumor HE CD31 4 PBS HE CD31 HE CD31 4 HE CD31 Fig 4 HE stained images and CD31 stained images of different treatment 13 ADC ADC 1 d ADC http / /xbzrb fzu edu cn

5 ADC ADC 3 d 14 d ADC 3 1 Xia Younan Li Weiyang Cobley C M et al Gold nanocages from synthesis to theranostic applications J Accounts of Chemical Research Kam N W S O Connell M Wisdom J A et al Carbon nanotubes as multifunctional biological transporters and near - infrared agents for selective cancer cell destruction J Proceedings of the National Academy of Sciences of the United States of America De La Zerda A Zavaleta C Keren S et al Carbon nanotubes as photoacoustic molecular imaging agents in living mice J Nature Nanotechnology Liu Zhuang Tabakman S Welsher K et al Carbon nanotubes in biology and medicine in vitro and in vivo detection imaging and drug delivery J Nano Research He Shijiang Song Bo Li Di et al A graphene nanoprobe for rapid sensitive and multicolor fluorescent DNA analysis J Advanced Functional Materials Jung J H Cheon D S Liu F et al A graphene oxide based immuno - biosensor for pathogen detection J Angewandte Chemie International Edition Yang K Zhang S Zhang G et al Graphene in mice ultrahigh in vivo tumor uptake and efficient photothermal therapy J Nano Letters Frankel T L Gian R K Jarnagin W R Preoperative imaging for hepatic resection of colorectal cancer metastasis J Journal of Gastrointestinal Oncology Heusner T A Kuemmel S Koeninger A et al Diagnostic value of diffusion - weighted magnetic resonance imaging DWI compared to FDG PET /CT for whole - body breast cancer staging J European Journal of Nuclear Medicine and Molecular Imaging Yang Kai Wan Jianmei Zhang Shuai et al The influence of surface chemistry and size of nanoscale graphene oxide on photothermal therapy of cancer using ultra - low laser power J Biomaterials Robinson J T Tabakman S M Liang Y et al Ultrasmall reduced graphene oxide with high near - infrared absorbance for photothermal therapy J Journal of the American Chemical Society Cai C J Xu M W Bao S J et al A green and facile route for constructing flower - shaped TiO 2 nanocrystals assembled on graphene oxide sheets for enhanced photocatalytic activity J Nanotechnology Green H N Crockett S D Martyshkin D V et al A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy - induced tumor regression J International Journal of Nanomedicine http / /xbzrb fzu edu cn

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