Hyaluronic acid-ceramide-based optical/MR dual imaging nanoprobe for cancer diagnosis.
Hyaluronic acid-ceramide (HACE)-based nanoprobes for magnetic resonance (MR) and optical imaging were developed for cancer diagnosis. Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to HACE for the chelation of gadolinium (Gd) as an MR contrast agent. Cy5.5 was also conjugated to the HACE backbone as a near-infrared fluorescence (NIRF) imaging dye. The self-assembled HACE-based nanoprobe, Cy5.5-HACE-DTPA-Gd, exhibited a uniformly distributed particle size and morphological shape. The HACE-based nanoprobe did not induce serious cytotoxicity in U87-MG (low expression of CD44 receptor) and SCC7 (high expression of CD44 receptor) cells. The cellular uptake efficiency of the HACE-based nanoprobe was higher in SCC7 cells than in U87-MG cells, indicating an HA-CD44 receptor interaction. In vitro MR signal enhancement of the HACE-based nanoprobe was confirmed compared with a commercial formulation (Magnevist). Moreover, in vivo MR contrast enhancement of the HACE-based nanoprobe in the tumor region was verified in an SCC7 tumor xenograft mouse model. The tumor targetability of the developed nanoprobe was monitored by an NIRF imaging study, and improved accumulation of the nanoprobe in the tumor region was observed. Therefore, this HACE-based dual-imaging nanoprobe can be used to make a more accurate diagnosis of cancer based on its passive and active tumor targeting strategies.
College of Pharmacy, Sunchon National University, Sunchon 540-950, Republic of Korea.
Hyun-Jong
HJ
Cho
Hong Yeol
HY
Yoon
Heebeom
H
Koo
Seung-Hak
SH
Ko
Jae-Seong
JS
Shim
Jee-Hyun
JH
Cho
Jae Hyung
JH
Park
Kwangmeyung
K
Kim
Ick Chan
IC
Kwon
Dae-Duk
DD
Kim
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002518:Ceramides / Q000737:chemistry / Q000493:pharmacokinetics; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis*
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D002518:Ceramides; D002614:Chelating Agents; D003287:Contrast Media; D006820:Hyaluronic Acid; D019786:Gadolinium DTPA