Choi Daeil, Jeon Sangmin, You Dong Gil, Um Wooram, Kim Jeong-Yeon, Yoon Hong Yeol, Chang Hyeyoun, Kim Dong-Eog, Park Jae Hyung, Kim Hyuncheol, Kim Kwangmeyung
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
Department of Chemical and Biomolecular Engineering and Interdisciplinary Program of Integrated Biotechnology, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.
Nanotheranostics. 2018 Jan 1;2(2):117-127. doi: 10.7150/ntno.18643. eCollection 2018.
Development of biopolymer-based imaging agents which can access rapidly and provide detailed information about the diseases has received much attention as an alternative to conventional imaging agents. However, development of biopolymer-based nanomaterials for tumor imaging still remains challenging due to their low sensitivity and image resolution. To surmount of these limitations, multimodal imaging agents have been developed, and they were widely utilized for theranostic applications. Herein, iodine containing echogenic glycol chitosan nanoparticles are developed for x-ray computed tomography (CT) and ultrasound (US) imaging of tumor diagnosis. X-ray CT/US dual-modal imaging probe was prepared by following below two steps. First, iodine-contained diatrizoic acid (DTA) was chemically conjugated to the glycol chitosan (GC) for the CT imaging. DTA conjugated GC (GC-DTA NPs) formed stable nanoparticles with an average diameter of 315 nm. Second, perfluoropentane (PFP), a US imaging agent, was physically encapsulated into GC-DTA NPs by O/W emulsion method yielding GC-DTA-PFP nanoparticles (GC-DTA-PFP NPs). The GC-DTA-PFP NPs formed nanoparticles in physiological condition, and they presented the strong x-ray CT, and US signals in phantom test in vitro. Importantly, GC-DTA-PFP NPs were effectively accumulated on the tumor site by enhanced permeation and retention (EPR) effects. Moreover, GC-DTA-PFP NPs showed x-ray CT, and US signals in tumor tissues after intratumoral and intravenous injection, respectively. Therefore, GC-DTA-PFP NPs indicated that x-ray CT/US dual-modal imaging using iodinated echogenic nanoparticles could be provided more comprehensive and accurate diagnostic information to diagnosis of tumor.
能够快速进入并提供有关疾病详细信息的基于生物聚合物的成像剂作为传统成像剂的替代品已备受关注。然而,基于生物聚合物的纳米材料用于肿瘤成像仍具有挑战性,因为它们的灵敏度和图像分辨率较低。为了克服这些限制,已开发出多模态成像剂,并广泛用于治疗诊断应用。在此,开发了含碘的超声造影剂乙二醇壳聚糖纳米颗粒用于肿瘤诊断的X射线计算机断层扫描(CT)和超声(US)成像。通过以下两个步骤制备X射线CT/US双模态成像探针。首先,将含碘的泛影酸(DTA)化学偶联到乙二醇壳聚糖(GC)上用于CT成像。DTA偶联的GC(GC-DTA NPs)形成平均直径为315nm的稳定纳米颗粒。其次,通过O/W乳液法将超声成像剂全氟戊烷(PFP)物理包封到GC-DTA NPs中,得到GC-DTA-PFP纳米颗粒(GC-DTA-PFP NPs)。GC-DTA-PFP NPs在生理条件下形成纳米颗粒,并且在体外模型测试中呈现出强烈的X射线CT和US信号。重要的是,GC-DTA-PFP NPs通过增强渗透和滞留(EPR)效应有效地聚集在肿瘤部位。此外,GC-DTA-PFP NPs分别在瘤内注射和静脉注射后在肿瘤组织中显示出X射线CT和US信号。因此,GC-DTA-PFP NPs表明使用碘化超声造影纳米颗粒的X射线CT/US双模态成像可为肿瘤诊断提供更全面和准确的诊断信息。