Skeleton labeled 13C-carbon nanoparticles for the imaging and quantification in tumor drainage lymph nodes

Abstract

Ping Xie,1 Qian Xin,2 Sheng-Tao Yang,3 Tiantian He,2,4 Yuanfang Huang,2 Guangfu Zeng,2,4 Maosheng Ran,2,5 Xiaohai Tang2 1State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, 2Chongqing Lummy Pharmaceutical Co., Ltd, Chongqing, 3College of Chemistry & Environment Protection Engineering, Southwest University for Nationalities, 4College of Life Sciences, Sichuan Normal University, 5State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Carbon nanoparticles (CNPs) have been widely used in tumor drainage lymph node (TDLN) imaging, drug delivery, photothermal therapy, and so on. However, during the theranostic applications, the accumulation efficiency of CNPs in target organs is unknown yet, which largely hinders the extension of CNPs into clinical uses. Herein, we prepared skeleton-labeled 13C-CNPs that had identical properties to commercial CNPs suspension injection (CNSI) for the imaging and quantification in TDLN. 13C-CNPs were prepared by arc discharge method, followed by homogenization with polyvinylpyrrolidone. The size distribution and morphology of 13C-CNPs were nearly the same as those of CNSI under transmission electron microscope. The hydrodynamic radii of both 13C-CNPs and CNSI were similar, too. According to X-ray photoelectron spectroscopy and infrared spectroscopy analyses, the chemical compositions and chemical states of elements were also nearly identical for both labeled and commercial forms. The skeleton labeling of 13C was reflected by the shift of G-band toward lower frequency in Raman spectra. 13C-CNPs showed competitive performance in TDLN imaging, where the three lymph nodes (popliteal lymph node, common iliac artery lymph node, and paraaortic lymph node) were stained black upon the injection into the hind extremity of mice. The direct quantification of 13C-CNPs indicated that 877 µg/g of 13C-CNPs accumulated in the first station of TDLN (popliteal lymph node). The second station of TDLN (common iliac artery lymph node) had even higher accumulation level (1,062 µg/g), suggesting that 13C-CNPs migrated efficiently along lymphatic vessel. The value decreased to 405 µg/g in the third station of TDLN (paraaortic lymph node). Therefore, the 13C-CNPs provided quantitative approach to image and quantify CNSI in biological systems. The implication in biomedical applications and biosafety evaluations of CNSI is discussed. Keywords: carbon nanoparticles suspension injection, 13C-labeling, isotope ratio mass spectroscopy, quantification, bioeffect of nanomaterials

Keywords

• carbon nanoparticles suspension injection
• 13C-labeling
• isotope ratio mass spectroscopy
• quantification
• bioeffect of nanomaterials