Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer

被引：120

作者：

Choi, Ki Young ^{[2
,3
]}

Jeon, Eun Jung ^{[4
]}

Yoon, Hong Yeol ^{[2
]}

Lee, Beom Suk ^{[2
,5
]}

Na, Jin Hee ^{[2
,6
]}

Min, Kyung Hyun ^{[2
,6
]}

Kim, Sang Yoon ^{[2
,5
]}

Myung, Seung-Jae ^{[7
,8
]}

Lee, Seulki ^{[3
]}

Chen, Xiaoyuan ^{[3
]}

Kwon, Ick Chan ^{[2
]}

Choi, Kuiwon ^{[2
]}

Jeong, Seo Young ^{[6
]}

Kim, Kwangmeyung ^{[2
]}

Park, Jae Hyung ^{[1
]}

机构：

[1] Sungkyunkwan Univ, Dept Polymer Sci & Engn, Theranost Macromol Res Ctr, Suwon 440746, South Korea

[2] Korea Inst Sci & Technol, Biomed Res Inst, Seoul 136791, South Korea

[3] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA

[4] Catholic Univ Korea, Sch Med, Dept Internal Med, Seoul, South Korea

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol, Seoul 138736, South Korea

[6] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea

[7] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Internal Med, Seoul 138736, South Korea

[8] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Digest Dis Res Inst, Seoul 138736, South Korea

来源：

BIOMATERIALS | 2012年 / 33卷 / 26期

关键词：

Hyaluronic acid; Nanoparticle; Theranostics; Irinotecan; Colon cancer; Tumor targeting; COLORECTAL-CANCER; 1ST-LINE TREATMENT; FLUOROURACIL; LEUCOVORIN; CARCINOMA; AGENT; CD44;

D O I：

10.1016/j.biomaterials.2012.05.029

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Colon cancer is the second leading cause of cancer-related death in the United States. The considerable mortality from colon cancer is due to metastasis to other organs, mainly the liver. In the management of colon cancer, early detection and targeted therapy are crucial. In this study, we aimed to establish a versatile theranostic system for early tumor detection and targeted tumor therapy by using poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) which can selectively accumulate in tumor tissue. For the diagnostic application, a near-infrared fluorescence (NIRF) imaging dye (Cy 5.5) was chemically conjugated onto the HA backbone of P-HA-NPs. After intravenous injection of Cy5.5-P-HA-NPs into the tumor-bearing mice, small-sized colon tumors as well as liver-implanted colon tumors were effectively visualized using the NIRF imaging technique. For targeted therapy, we physically encapsulated the anticancer drug, irinotecan (IRT), into the hydrophobic cores of P-HA-NPs. Owing to their notable tumor targeting capability, IRT-P-HA-NPs exhibited an excellent antitumor activity while showing a reduction in undesirable systemic toxicity. Importantly, we demonstrated the theranostic application using Cy5.5-P-HA-NPs and IRT-P-HA-NPs in orthotopic colon cancer models. Following the systemic administration of Cy5.5-P-HA-NPs, neoplasia was clearly visualized, and the tumor growth was effectively suppressed by intravenous injection of IRT-P-HA-NPs. It should be emphasized that the therapeutic responses could be simultaneously monitored by Cy5.5-P-HA-NPs. Our results suggest that P-HA-NPs can be used as a versatile theranostic system for the early detection, targeted therapy, and therapeutic monitoring of colon cancer. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：6186 / 6193

页数：8