Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer.
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.
Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
Ki Young
KY
Choi
Eun Jung
EJ
Jeon
Hong Yeol
HY
Yoon
Beom Suk
BS
Lee
Jin Hee
JH
Na
Kyung Hyun
KH
Min
Sang Yoon
SY
Kim
Seung-Jae
SJ
Myung
Seulki
S
Lee
Xiaoyuan
X
Chen
Ick Chan
IC
Kwon
Kuiwon
K
Choi
Seo Young
SY
Jeong
Kwangmeyung
K
Kim
Jae Hyung
JH
Park
D000818:Animals; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D019073:HT29 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D011092:Polyethylene Glycols; D006820:Hyaluronic Acid