TY - JOUR
T1 - Identification of Two Novel Small Compounds that Inhibit Liver Cancer Formation in Zebrafish and Analysis of Their Conjugation to Nanodiamonds to Further Reduce Toxicity
AU - Tseng, Po Han
AU - Sie, Zong Lin
AU - Liu, Meng Chieh
AU - Lin, Han Syuan
AU - Yang, Wan Yu
AU - Lin, Ting Yu
AU - Hsieh, Hsing Pang
AU - Hung, Shih Che
AU - Cheng, Chia Liang
AU - Wang, Horng Dar
AU - Chang, Hsin Hou
AU - Yuh, Chiou Hwa
N1 - Funding Information:
P.-H.T. and Z.-L.S. contributed equally to this work. P.-H.T. and Z.-L.S. carried out their thesis research under the auspices of the Graduate Program of Biotechnology in Medicine, National Tsing Hua University and National Health Research Institutes. This work was supported by the Buddhist Tzu Chi Medical Foundation (TW) (C.-H.Y. and H.-H.C., under grant numbers TC-NHRI105-02, TCMMP104-06, TCMMP108-04, and TCAS-108-01) and Taiwan's Ministry of Health and Welfare (MOHW), Advance Medical Plan (108-0324-01-19-07) to C.-H.Y. The authors would like to thank the Taiwan Zebrafish Core Facility at NTHU-NHRI (TZeTH) for providing fish lines and resources; TZeTH is supported by a grant from the MOST (105-2319-B-400-001). The authors also thank NHRI IBEN Service (NIS) for providing Field Emission-Scanning Electron Microscopy (FE-SEM) imaging for the NDs and derivatives. The authors also would like to thank Brian Wang for his art design for the Table of Contents (TOC) figure.
Publisher Copyright:
© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Liver cancer, which is ranked fourth in cancer-related mortality worldwide, lacks effective therapeutic treatments. The development of new targeted therapies for liver cancer is urgently needed. The zebrafish is an excellent preclinical model organism for drug screening. Therefore, in a zebrafish model, hundreds of small molecules are screened, and two compounds (LIB1O0078 and LIB1O0144) are identified as the strongest inducers of antiangiogenic effects without side effects. LIB1O0078 exhibits better antiproliferation ability, and LIB1O0144 has better antimigration ability, as shown by xenotransplantation assays. Furthermore, LIB1O0078 and LIB1O0144 exhibit anti-HCC effects after retro-orbital injection into adult Tg(fabp10a:HBx,Src, p53-) triple transgenic fish with obesity and liver cancer. Because of the embryonic toxicity induced by these compounds, they are conjugated with nanodiamonds (ND), which are highly biocompatible function-based carriers. ND-coated small molecules not only reduce the embryonic toxicity and hepatotoxicity of the compounds, also exhibit better anti-HCC effects when administered by oral gavage in adult Tg(fabp10a:HBx,Src, p53-) fish with obesity and liver cancer. This study integrates nanotechnology and biomedical technology, identifies new potential anticancer drugs, and demonstrates the effectiveness of coating them on nanodiamonds in vivo. Facilitated by such a rapid zebrafish screening system, new anticancer drugs can be identified in a personalized and timely manner.
AB - Liver cancer, which is ranked fourth in cancer-related mortality worldwide, lacks effective therapeutic treatments. The development of new targeted therapies for liver cancer is urgently needed. The zebrafish is an excellent preclinical model organism for drug screening. Therefore, in a zebrafish model, hundreds of small molecules are screened, and two compounds (LIB1O0078 and LIB1O0144) are identified as the strongest inducers of antiangiogenic effects without side effects. LIB1O0078 exhibits better antiproliferation ability, and LIB1O0144 has better antimigration ability, as shown by xenotransplantation assays. Furthermore, LIB1O0078 and LIB1O0144 exhibit anti-HCC effects after retro-orbital injection into adult Tg(fabp10a:HBx,Src, p53-) triple transgenic fish with obesity and liver cancer. Because of the embryonic toxicity induced by these compounds, they are conjugated with nanodiamonds (ND), which are highly biocompatible function-based carriers. ND-coated small molecules not only reduce the embryonic toxicity and hepatotoxicity of the compounds, also exhibit better anti-HCC effects when administered by oral gavage in adult Tg(fabp10a:HBx,Src, p53-) fish with obesity and liver cancer. This study integrates nanotechnology and biomedical technology, identifies new potential anticancer drugs, and demonstrates the effectiveness of coating them on nanodiamonds in vivo. Facilitated by such a rapid zebrafish screening system, new anticancer drugs can be identified in a personalized and timely manner.
UR - http://www.scopus.com/inward/record.url?scp=85083512788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083512788&partnerID=8YFLogxK
U2 - 10.1002/adtp.201900105
DO - 10.1002/adtp.201900105
M3 - Article
AN - SCOPUS:85083512788
SN - 2366-3987
VL - 2
JO - Advanced Therapeutics
JF - Advanced Therapeutics
IS - 12
M1 - 1900105
ER -