br Author contributions br Lin Xu
Lin Xu, Guangfu Jin and Binhui Ren designed the study. Biqing Zhu, Yinpeng Pan and Xiufen Zheng performed the experiment. Quanli Zhang and Yaqin Wu were responsible for graphics. Jing Luo and Qian Li wrote the manuscript. Emei Lu made statistical analysis.
This research was supported by the National Natural Science Foun-dation of China (81672869), Jiangsu Provincial Special Program of Med-ical Science Funding (BL2012030), Jiangsu Provincial Science Foundation (BK20161596), Jiangsu Provincial Medical Outstanding Tal-ent (Lin Xu) and Jiangsu Provincial Medical Youth Talent (Binhui Ren, QNRC2016657).
 M.P. Tremblay, V.E. Armero, A. Allaire, S. Boudreault, C. Martenon-Brodeur, M. Durand, E. Lapointe, P. Thibault, M. Tremblay-Letourneau, J.P. Perreault, M.S. Scott, M. Bisaillon, Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma, BMC Genomics 17 (2016) 683.
Contents lists available at ScienceDirect
Biosensors and Bioelectronics
journal homepage: www.elsevier.com/locate/bios
A colorimetric immunosensor based on self-linkable dual-nanozyme for T
ultrasensitive EPZ031686 cancer diagnosis and prognosis monitoring
Chen Penga,1, Mu-Yi Huab,c,1, Nan-Si Lia,d, Ying-Pei Hsua, Ying-Tzu Chena, Cheng-Keng Chuange,f, See-Tong Pange,f, , Hung-Wei Yanga,
a Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
b Department of Chemical and Materials Engineering, Biosensor Group, Biomedical Engineering Research Center; and Healthy Aging Research Center, Chang Gung University, Taoyuan 33302, Taiwan
c Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan
d Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
e Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan
f School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Magnetic graphene oxide
ApoA1 immunosensing Signal amplification
Bladder cancer diagnosis
We developed self-linkable Prussian blue (PB)-incorporated magnetic graphene oxide (PMGO) as a peroxidase-mimicking nanozyme with high oxidizability to 3,3′,5,5′-tetramethylbenzidine (TMB), which generates sig-nificant absorption intensity for the colorimetric immunosensing of apolipoprotein A1 (ApoA1) in early bladder cancer (BC) diagnosis and prognosis monitoring. The ultrasensitive immunosensor was constructed using an ApoA1 antibody (AbApoA1)-functionalized chip (biochipApoA1) and self-linkable peroxidase-mimicking, PB-in-corporated magnetic graphene oxide (PMGO). After incubating the sample and capturing ApoA1 proteins cap-tured on the biochipApoA1, the PMGO was functionalized with AbApoA1, and then mouse IgG (PMGO-1), rabbit anti-mouse IgG antibody (PMGO-2), and goat anti-rabbit IgG antibody (PMGO-3) were added together. We envisioned that each captured ApoA1 protein would allow the retention of a large amount of PMGO through a self-linking process to amplify the colorimetric signal of TMB in the presence of H2O2. The linear detection range could be obviously widened in the presence of self-linkable PMGO—from 0.05 ng/mL to 100 ng/mL—compared with the group without signal amplification (from 1 ng/mL to 100 ng/mL). Our immunosensor analysis of ApoA1 in the urine of BC patients and healthy individuals was highly correlated with enzyme-linked immunosorbent assay measurements; moreover, the ApoA1 concentrations of patients with high-grade BC were significantly higher than those of patients with low-grade BC. After standard clinical treatment, a significant drop of ApoA1 concentration occurred in urine that was lower than the cut-oﬀ concentration, suggesting potential clinical applications of the new self-linkable PMGO-generating colorimetric immunosensor in early BC diagnosis and prognosis monitoring.