International Journal of Nanomedicine (Aug 2021)
Radiolabeling and Preliminary Evaluation of 99mTc-Labeled DNA Cube Nanoparticles as Potential Tracers for SPECT Imaging
Abstract
Xiaoyan Duan,1 Yiri Du,1 Chunmei Wang,1,2 Zhenfeng Zhao,1,2 Chao Li,1 Jianbo Li1,2 1Inner Mongolia Medical University Affiliated Hospital, Hohhot, 010050, People’s Republic of China; 2Inner Mongolia Key Laboratory of Molecular Imaging, Hohhot, 010050, People’s Republic of ChinaCorrespondence: Jianbo LiInner Mongolia Medical University Affiliated Hospital, No. 1 Tongdao North Street, Hohhot, 010050, People’s Republic of ChinaTel/ Fax +86 471 345 1574Email [email protected]: DNA nanostructures, with the advantages of structural designability and spatial addressability, have shown a great potential in the field of drug delivery and bio-medicine. Herein, we aimed to prepare technetium-99m radiolabeled DNA cube nanoparticles (99mTc-DCN) and expect to build a DCN-based drug carrier and nuclear medicine imaging platform.Methods: DCN could be readily assembled with 6 designed DNA oligonucleotides at an equal mole ratio in a single annealing procedure. 99mTc-MAG3-ssDNA (A20) was obtained by labeling MAG3-ssDNA (A20) with technetium-99m by using a stannous chloride reduction method. 99mTc-DCN was prepared by hybridize DCN with side chains (T20-DCN) with 99mTc-MAG3-ssDNA (A20). The biodistribution study and SPECT/CT imaging were conducted on KM mice.Results: DCN was successfully assembled, and as-prepared DCN was characterized by native polyacrylamide gel electrophoresis, atomic force microscope and fluorescence resonance energy transfer. The size of DCN was about 5 nm. The radiolabeling yield of 99mTc-MAG3-ssDNA (A20) was approximately 90% by radio thin-layer chromatography. T20-DCN mixed with 99mTc-MAG3-ssDNA (A20) in PBS could generate 99mTc-DCN upon hybridization. The retention time (RT) of 99mTc-MAG3-ssDNA (A20) was at ∼ 22 min, and the RT of as-prepared 99mTc-DCN was at ∼ 12 min by radio-HPLC. The results from biodistribution study and SPECT/CT imaging showed that a significant proportion of DCNs were metabolized through the liver and kidney. Intestine exhibited a relatively indicative signal as well, which might be explained by the enterohepatic circulation of DCN via the liver and gallbladder.Conclusion: We have successfully prepared 99mTc-DCN as a SPECT/CT imaging probe via the side-chain hybridization strategy. The probe was metabolized mainly by the liver and excreted primarily to the bladder. Due to the superior properties of DNA cube nanoparticles, we believe DCN may potentially be translated into a preclinical setting for diagnosis and treatment of cancer-related diseases.Keywords: DNA cube nanoparticles, Tc-99m labeling, biodistribution, SPECT/CT imaging
