Abstract
Colorectal cancer is one of the major causes of cancer-related death in Taiwan and worldwide. Patients with peritoneal metastasis from colorectal cancer have reduced overall survival and poor prognosis. Hybrid protein-inorganic nanoparticle systems have displayed multifunctional applications in solid cancer theranostics. In this study, a gold nanocore-encapsulated human serum albumin nanoparticle (Au@HSANP), which is a hybrid protein-inorganic nanoparticle, and its radioactive surrogate 111In-labeled Au@HSANP (111In-Au@HSANP), were developed and their biological behaviors were investigated in a tumor/ascites mouse model. 111In-Au@HSANP was injected either intravenously (iv) or intraperitoneally (ip) in CT-26 tumor/ascites-bearing mice. After ip injection, a remarkable and sustained radioactivity retention in the abdomen was noticed, based on microSPECT images. After iv injection, however, most of the radioactivity was accumulated in the mononuclear phagocyte system. The results of biodistribution indicated that ip administration was significantly more effective in increasing intraperitoneal concentration and tumor accumulation than iv administration. The ratios of area under the curve (AUC) of the ascites and tumors in the ip-injected group to those in the iv-injected group was 93 and 20, respectively. This study demonstrated that the ip injection route would be a better approach than iv injections for applying gold-albumin nanoparticle in peritoneal metastasis treatment.
Highlights
Colorectal cancer is the most common type of gastrointestinal cancer, accounting for over 9% of all cancer cases [1]
The results of the pharmacokinetics and biodistribution studies revealed that iv administration of Au@HSANP with an average size of 213.3 ± 32.9 nm exhibited a short distribution half-life (T1/2α = 0.05 h) and a much longer elimination half-life (T1/2β = 19.7 h)
Kinoshita et al reported that nearly 20%ID/g of Abraxane® (130 nm) accumulated in the liver at one hour post iv injection, while less than 1%ID/g accumulates in tumor lesions in computed tomography (CT)-26 tumor-bearing nu/nu mice [46]
Summary
Colorectal cancer is the most common type of gastrointestinal cancer, accounting for over 9% of all cancer cases [1]. According to annual reports issued by the Ministry of Health and Welfare in Taiwan, colorectal cancer is second only to breast cancer in incidence and ranks third in mortality. It is the fourth most common cause of death throughout the world [2]. Peritoneal metastasis is one of the phenomena in patients suffering from colorectal, gastric or ovarian cancer at the late phase [3,4,5,6]. Nanoparticles (NPs) can encapsulate poorly soluble drugs, fluorescent dyes, and imaging contrast agents and have multifunctional biological applications. Based on the rapid development of nanotechnology, nanoparticle (NP)-based theranostic agents, called nanotheranostic agents, have provided an opportunity to achieve individualized treatment [11]
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