Nano-graphene oxide composite for in vivo imaging

Sung-Chan Jang1 Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon;2 Biotechnology Research Division

Sung-Min Kang1 Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon

Jun Young Lee3 Radiation Instrumentation Research Division, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup

Seo Yeong Oh1 Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon

AT Ezhil Vilian4 Department of Energy and Materials Engineering, Dongguk University, Seoul

Ilsong Lee1 Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon;2 Biotechnology Research Division

Young-Kyu Han4 Department of Energy and Materials Engineering, Dongguk University, Seoul

Jeong Hoon Park3 Radiation Instrumentation Research Division, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup

Wan-Seob Cho5 Laboratory of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan

Changhyun Roh2 Biotechnology Research Division;6 Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology (UST), Daejeon, Republic of KoreaCorrespondence[email protected]

Yun Suk Huh1 Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, IncheonCorrespondence[email protected]

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Abstract

Introduction

Positron emission tomography (PET) tracers has the potential to revolutionize cancer imaging and diagnosis. PET tracers offer non-invasive quantitative imaging in biotechnology and biomedical applications, but it requires radioisotopes as radioactive imaging tracers or radiopharmaceuticals.

Method

This paper reports the synthesis of ¹⁸F-nGO-PEG by covalently functionalizing PEG with nano-graphene oxide, and its excellent stability in physiological solutions. Using a green synthesis route, nGO is then functionalized with a biocompatible PEG polymer to acquire high stability in PBS and DMEM.

Results and discussion

The radiochemical safety of ¹⁸F-nGO-PEG was measured by a reactive oxygen species and cell viability test. The biodistribution of ¹⁸F-nGO-PEG could be observed easily by PET, which suggested the significantly high sensitivity tumor uptake of ¹⁸F-nGO-PEG and in a tumor bearing CT-26 mouse compared to the control. ¹⁸F-nGO-PEG was applied successfully as an efficient radiotracer or drug agent in vivo using PET imaging. This article is expected to assist many researchers in the fabrication of ¹⁸F-labeled graphene-based bio-conjugates with high reproducibility for applications in the biomedicine field.

Keywords:

Supplementary materials

Figure S1 CT26-bearing nude mice.

Note: Tumors were grown in the right thighs of the nude mice (20–25 g) by injecting tumor cells.

Figure S2 Conjugation chemistry between nGO and ¹⁸F⁻.

Notes: The ¹⁸F⁻ is connected to the nGO. The hydrogen atoms bonding on the organic macromolecules (C–H and O–H) are easily substituted by fluorine atoms. Abbreviation: nGO, nano-graphene oxide.

Figure S2 Conjugation chemistry between nGO and 18F−.Notes: The 18F− is connected to the nGO. The hydrogen atoms bonding on the organic macromolecules (C–H and O–H) are easily substituted by fluorine atoms. Abbreviation: nGO, nano-graphene oxide.

Figure S3 ¹⁸F was injected intravenously into the female mice and images monitored at different times.

Note: PET images of tumor-bearing mice at (A) 15, (B) 30, (C) 60, and (D) 120 min after intravenous injection. No signal was observed in tumor cells under in vivo conditions.

Abbreviation: SUV, standardized uptake value.

Figure S3 18F was injected intravenously into the female mice and images monitored at different times.Note: PET images of tumor-bearing mice at (A) 15, (B) 30, (C) 60, and (D) 120 min after intravenous injection. No signal was observed in tumor cells under in vivo conditions.Abbreviation: SUV, standardized uptake value.

Figure S4 ¹⁸F-nGO was injected intravenously into the female mice and images monitored at different times.

Note: PET images of tumor-bearing mice at (A) 15, (B) 30, (C) 60, and (D) 120 min after intravenous injection. No signal was observed in tumor cells under in vivo conditions.

Abbreviation: SUV, standardized uptake value.

Figure S4 18F-nGO was injected intravenously into the female mice and images monitored at different times.Note: PET images of tumor-bearing mice at (A) 15, (B) 30, (C) 60, and (D) 120 min after intravenous injection. No signal was observed in tumor cells under in vivo conditions.Abbreviation: SUV, standardized uptake value.

Figure S5 ¹⁸F-nGO-PEG was injected intravenously into the female mice and images monitored at different times (15, 30, and 60 minutes).

Notes: An intact ¹⁸F-nGO-PEG tumor and bioimaging of tumor cell were monitored. PET images of tumor-bearing mice at (A) 15, (B) 30, and (C) 60 after intravenous injection. CT26 was taken up rapidly into the early endosomes and lysosomes of CT26 tumor cells within 15 minutes.

Abbreviations: nGO, nano-graphene oxide; PEG, polyethylene glycol.

Figure S5 18F-nGO-PEG was injected intravenously into the female mice and images monitored at different times (15, 30, and 60 minutes).Notes: An intact 18F-nGO-PEG tumor and bioimaging of tumor cell were monitored. PET images of tumor-bearing mice at (A) 15, (B) 30, and (C) 60 after intravenous injection. CT26 was taken up rapidly into the early endosomes and lysosomes of CT26 tumor cells within 15 minutes.Abbreviations: nGO, nano-graphene oxide; PEG, polyethylene glycol.

Acknowledgments

This work was supported by the Radiation Fusion Technology Program (2015M2A2A6A02045262(3)) from the Nuclear Research R&D Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT, Republic of Korea. It was also partially supported from the Nuclear Research R&D Program (2015M2B2A4028536 and 2016M2B2A4912204) through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT, Republic of Korea. Special thanks is given to Dr Min Goo Hur, team leader of Cyclotron from Radiation Instrumentation Research Division and Dr Jin-Woo Lee from Safety Management Team, KAERI for their kind support in facility use.

Disclosure

The authors report no conflicts of interest in this work.