Acetylated Polyethylenimine-Entrapped Gold Nanoparticles Enable

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Biological and Environmental Phenomena at the Interface

Acetylated Polyethylenimine-Entrapped Gold Nanoparticles Enable Negative CT Imaging of Orthotopic Hepatic Carcinoma Benqing Zhou, Zhijuan Xiong, Peng Wang, Chen Peng, Mingwu Shen, and Xiangyang Shi Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b01669 • Publication Date (Web): 29 Jun 2018 Downloaded from http://pubs.acs.org on June 30, 2018

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Langmuir

Acetylated Polyethylenimine-Entrapped Gold Nanoparticles Enable Negative CT Imaging of Orthotopic Hepatic Carcinoma

Benqing Zhoua, b, Zhijuan Xiongb, Peng Wangb, Chen Penga*, Mingwu Shenb*, Xiangyang Shia, b, c*

a

Department of Radiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, P. R. China b

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China

c

CQM - Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal

KEYWORDS: gold nanoparticles; polyethylenimine; negative CT imaging; hepatic carcinoma; acetylation

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ABSTRACT Developing an effective computed tomography (CT) contrast agent is still a challenging task for precise diagnosis of hepatic carcinoma (HCC). Here, we present the use of acetylated polyethylenimine

(PEI)-entrapped gold

nanoparticles (Ac-PE-AuNPs) without antifouling

modification for negative CT imaging of HCC. PEI was firstly linked to fluorescein isothiocyanate (FI) and then utilized as a vehicle for entrapment of AuNPs. The particles were then acetylated to reduce its positive surface potential. The designed Ac-PE-AuNPs were characterized by various techniques. We find that the Ac-PE-AuNPs with a uniform size distribution (mean diameter = 2.3 nm) are colloidally stable and possess low-toxicity in the studied range of concentration. Owing to the fact that the particles without additional antifouling modification were mainly gathered in liver, the Ac-PE-AuNPs could greatly improve the CT contrast enhancement of normal liver, whereas poor CT contrast enhancement appeared in HCC. As a result, HCC could be easily and precisely diagnosed. The designed Ac-PE-AuNPs were demonstrated to have biocompatibility through in vivo biodistribution and histological studies, hence holding an enormous potential to be adopted as an effective negative CT contrast agent for diagnosis of hepatoma carcinoma.

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Langmuir

INTRODUCTION Hepatic carcinoma (HCC) has been considered as the fifth common cancer type and ranked as the third leading cause of cancer deaths in the world.1-2 Molecular imaging of HCC currently includes computed tomography (CT),3-5 ultrasonography,6-7 nuclear medicine imaging,8-9 and magnetic resonance imaging.10-12 X-ray-based CT has been regarded as one of the most common molecular imaging methods, which affords a deep tissue penetration and high three-dimensional resolution.13-15 Because of the inherently low sensitivity in CT imaging of soft tissues, administration of a certain amount of contrast agent is frequently required for accurate diagnosis with high contrast. Currently, small iodinated molecular CT contrast agents are routinely utilized in clinical settings. However, these iodinated compounds are generally confronted with problems of short imaging time (e.g., ultravist,