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Yue Shang,1,* Hui Zhang,2,* Yajia Cheng,3 Peipei Cao,3 Jianlin Cui,3 Xuebo Yin,4 Saijun Fan,1 Yuhao Li5 1Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China; 2Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China; 3Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People’s Republic of China; 5Beijing Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhao Li, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China, Tel +86-10-83198269, Email liyuhao@xwh.ccmu.edu.cnBackground: Hepatocellular carcinoma (HCC), arising from hepatocytes, is the most common primary liver cancer. It is urgent to develop novel therapeutic approaches to improve the grim prognosis of advanced HCC. 10-hydroxycamptothecin (HCPT) has good antitumor activity in cells; however, its hydrophobicity limits its application in the chemotherapy of HCC. Recently, nanoscale porphyrin metal-organic frameworks have been used as drug carriers due to their low biotoxicity and photodynamic properties.Methods: Nanoscale zirconium porphyrin metal-organic frameworks (NMOFs) were coated with arginine-glycine-aspartic acid (RGD) peptide to prepare NMOFs-RGD first. The HepG2 cell line, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of NMOFs-RGD both in vitro and in vivo. Then, NMOFs were used as the skeleton, HCPT was assembled into the pores of NMOFs, while RGD peptide was wrapped around to synthesize a novel kind of nanocomposites, HCPT@NMOFs-RGD. The tissue distribution and chemo- and p

Peipei Cao,1 Hao Zhang,2 Huiling Meng,1 Yajia Cheng,1 Haiqi Xu,3 Siwen Zang,1 Zongjin Li,1 Jianlin Cui,1,4 Yuhao Li1,5 1Nankai University School of Medicine, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Faculty of Life Science, University of Liverpool, Liverpool, UK; 4Medical International Collaborative Innovation Center, Nankai University School of Medicine, Tianjin, People’s Republic of China; 5Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Yuhao LiDepartment of Pathology, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email liyuhao@nankai.edu.cnJianlin CuiMedical International Collaborative Innovation Center, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 23502554Email cuijianlin@nankai.edu.cnBackground: The myelin sheath can be damaged by genetic and/or environmental factors, leading to demyelinating diseases, for which effective treatments are lacking. Recently, cyclooxygenase-2 (COX-2) overexpression was detected in demyelinating lesions both in patients and animal models, opening an avenue for promoting endogenous remyelination. The aim of this study was to investigate the therapeutic effect of celecoxib, a selective COX-2 inhibitor, against demyelination in a zebrafish model.Methods: The biotoxicity of celecoxib was evaluated on zebrafish embryos. Metronidazole was used to deplete the oligodendrocytes in Tg (mbp:nfsB-egfp) transgenic fish. Celecoxib was then administered both in larvae and adults. The regeneration of the myelin sheath and the underlying mechanisms were explored by immunohistochemistry, flow cytometry, Western blot analysis, quantitative real-time polymerase chain reaction, and behavioral t

Yajie Wang,1,2,* Wei Liu,3,4,* Bo Yuan,1,2 Xuebo Yin,3 Yiming Li,1 Zongjin Li,1 Jianlin Cui,1 Xiaoyong Yuan,2 Yuhao Li1,5 1Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin 300071, People’s Republic of China; 2Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Nankai University Eye Hospital, Tianjin 300020, People’s Republic of China; 3State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University College of Chemistry, Tianjin 300071, People’s Republic of China; 4Tianjin University School of Science, Tianjin 300072, People’s Republic of China; 5Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin 300192, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhao LiTianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, 94 Weijin Road, Tianjin 300071, People’s Republic of ChinaTel +86 22 2350 2554Email liyuhao@nankai.edu.cnXiaoyong YuanTianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, 4 Gansu Road, Tianjin 300020, People’s Republic of ChinaTel +86 22 2731 3336Email yuanxy_cn@hotmail.comBackground: Photoreceptor degeneration is one of the most refractory oculopathy in the world, leading to vision loss in severe cases. Methyprednisolone is one of the most commonly prescribed medications for the treatment of retinal degenerative diseases, either by oral administration or repeated intraocular injections. However, the efficacy was unsatisfactory due to its systemic or local side effects and short retention time within the retina.Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was synthesized and characterized. The biotoxicity and imaging capability

Yang Chen,1,2,* Wei Liu,3,4,* Yue Shang,1,2 Peipei Cao,1,2 Jianlin Cui,1,2 Zongjin Li,1 Xuebo Yin,3 Yuhao Li1,2 1Nankai University School of Medicine, Tianjin, China; 2Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical International Collaborative Innovation Center, Nankai University, Tianjin, China; 3State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, China; 4School of Science, Tianjin University, Tianjin, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and severely threatens human health. Since the prognosis of advanced HCC remains poor, there is an urgent need to develop new therapeutic approaches. Porphyrin metal-organic frameworks are a class of porous organic-inorganic hybrid functional materials with good biocompatibility. Methods: Gadolinium-porphyrin metal-organic frameworks were used as a skeleton for folic acid (FA) conjugation to synthesize a novel type of nanoparticle, denoted as folic acid-nanoscale gadolinium-porphyrin metal-organic frameworks (FA-NPMOFs). The FA-NPMOFs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric-differential thermal analysis. The biotoxicity and imaging capability of the FA-NPMOFs were determined using HepG2 cells and embryonic and larval zebrafish. The delivery and photodynamic therapeutic effect of FA-NPMOFs were explored in transgenic zebrafish with doxycycline-induced HCC. Results: FA-NPMOFs were spherical in structure with good dispersion and water solubility. They showed low biotoxicity, emitted bright red fluorescence, and exhibited an excellent magnetic resonance imaging capability, both in vitro and in vivo. Meanwhile, the FA-NPMOFs exhibited a strong affinity for folate receptor (FR)-expressing cells and were de

Yan Sun, Gong Zhang, Zizi He, Yajie Wang, Jianlin Cui, Yuhao Li Department of Pathology, Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, People’s Republic of China Abstract: Copper oxide nanoparticles (CuO NPs) are used for a variety of purposes in a wide range of commercially available products. Some CuO NPs probably end up in the aquatic systems, thus raising concerns about aqueous exposure toxicity, and the impact of CuO NPs on liver development and neuronal differentiation remains unclear. In this study, particles were characterized using Fourier transform infrared spectra, scanning electron microscopy, and transmission electron microscopy. Zebrafish embryos were continuously exposed to CuO NPs from 4 hours postfertilization at concentrations of 50, 25, 12.5, 6.25, or 1 mg/L. The expression of gstp1 and cyp1a was examined by quantitative reverse transcription polymerase chain reaction. The expression of tumor necrosis factor alpha and superoxide dismutase 1 was examined by quantitative reverse transcription polymerase chain reaction and Western blotting. Liver development and retinal neurodifferentiation were analyzed by whole-mount in situ hybridization, hematoxylin–eosin staining, and immunohistochemistry, and a behavioral test was performed to track the movement of larvae. We show that exposure of CuO NPs at low doses has little effect on embryonic development. However, exposure to CuO NPs at concentrations of 12.5 mg/L or higher leads to abnormal phenotypes and induces an inflammatory response in a dose-dependent pattern. Moreover, exposure to CuO NPs at high doses results in an underdeveloped liver and a delay in retinal neurodifferentiation accompanied by reduced locomotor ability. Our data demonstrate that short-term exposure to CuO NPs at high doses shows hepatotoxicity and neurotoxicity in zebrafish embryos and larvae. Keywords: copper oxide nanoparticles