Browsing by Author "Dayananda, Kasala"

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In vivo MR/optical imaging for gastrin releasing peptide receptor of prostate cancer tumor using Gd-TTDA-NP-BN-Cy5.5
(2011-02-01)
Lin, Ying-Hsiu
;
Dayananda, Kasala
;
Chen, Chiao-Yun
;
Liu, Gin-Chung
;
Luo, Tsai-Yueh
Magnetic resonance imaging (MRI) has become the leading imaging tool for providing fine anatomical and physiology details. Optical imaging is offering a sensitive and specific method for in vivo molecular imaging of targeting molecules. The goal of this study is to design, synthesize, and characterize a new target-specific dual contrast agent for MR and optical imaging. Hence, [Gd(TTDA-NP)(H(2)O)](2-) was prepared and characterized. In addition, an 8-amino acid Bombesin analogue (BN) peptide substrate, which can target prostate, breast, and colon cancer, was synthesized by solid-phase peptide synthesis and subsequently conjugated with [Gd(TTDA-NP)(H(2)O)](2-) to form BN conjugated Gd-TTDA-NP-BN. The water-exchange rate (ke(ex)(298)) for [Gd(TTDA-NP)(H(2)O)](2-) (110 x 10(6) s(-1)) is significantly higher than that of [Gd(DTPA) (H(2)O)](2-) complex and the rotational correlation time (tau(R)) for [Gd(TTDA-NP)(H(2)O)](2-) (145 ps) is also higher than those of [Gd(TTDA)(H(2)O)](2-) (104 ps) and [Gd(DTPA)(H(2)O)](2-) (103 ps). The Gd-TTDA-NP-BN shows remarkable high relaxivity (7.12 mM(-1) s(-1)) comparing to that of [Gd(TTDA-NP)(H(2)O)](2-). The fluorescence studies showed that the Gd-TTDA-NP-BN could efficiently enter PC-3 cells. Additionally, the human cancer cells xenografts using Gd-TTDA-NP-BN-Cy5.5 as an optical imaging probe clearly visualized subcutaneous PC-3 tumor and demonstrated its targeting ability to the gastrin releasing peptide (GRP) receptor overexpression. Furthermore, the biodistribution studies demonstrated significantly high tumor uptake (25.97 +/- 1.07% ID/g) and high tumor-to-normal tissue ratios at one hour post-injection of Gd-TTDA-NP-BN-Cy5.5 in the animal model. These results suggest that the Gd-1TDA-NP-BN-Cy5.5 is a superior probe for in vivo optical imaging. Importantly, the MR imaging studies showed notable signal enhancement (44.9 +/- 4.2%) on the tumor, indicating a high level accumulation of the contrast agent within the PC-3 tumor sites. Hence, targeting of prostate cancer cells was observed under in vitro and in vivo MR imaging studies using Gd-TTDA-NP-BN contrast agent. We conclude that Gd-TTDA-NP-BN and Gd-TTDA-NP-BN-Cy5.5 can be potentially used as the contrast agents for targeting GRP receptor oyerexpressing cells and tumors. (C) 2010 Elsevier Ltd. All rights reserved.
Sensitivity evaluation of rhodamine B hydrazide towards nitric oxide and its application for macrophage cells imaging
(2011-12-05)
Wu, Chi-Ming
;
Chen, Yen-Hao
;
Dayananda, Kasala
;
Shiue, Tsun-Wei
;
Hung, Chen-Hsiung
A colorless and non-fluorescent rhodamine derivative, rhodamine B hydrazide (RH), is applied to detect nitric oxide and form fluorescent rhodamine B (RB). The reaction mechanism of RH with NO is proposed in this study. The probe shows good stability over a broad pH range (pH > 4). Furthermore, fluorescence intensity of RH displays an excellent linearity to the NO concentration and the detection limit is as low as 20 nM. A 1000-fold fluorescence turn-on from a dark background was observed. Moreover, the selectivity study indicated that the fluorescence intensity increasing in the presence of NO was significantly higher than those of other reactive oxygen/nitrogen species. In exogenously generated NO detection study, clear intracellular red fluorescence was observed in the presence of S-nitroso-N-acetyl-D,L-penicillamine (SNAP, a kind of NO releasing agent). In endogenously generated NO detection study, increasing incubation time of RH with lipopolysaccharied (LPS) pre-treated cells could obtain a highly fluorescent cell image. These cell imaging results demonstrated that RH can efficiently penetrate into Raw 264.7 cells and be used for detection of exogenously and endogenously generated nitric oxide. (C) 2011 Elsevier B.V. All rights reserved.
Targeted RGD nanoparticles for highly sensitive in vivo integrin receptor imaging
(2012-01-01)
Lin, Ren-Yen
;
Dayananda, Kasala
;
Chen, Ting-Jung
;
Chen, Chiao-Yun
;
Liu, Gin-Chung
A new magnetic resonance imaging (MRI) contrast bearing RGD peptide is reported. In this study, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with various sizes were prepared. Particles sizes between 6 and 13?nm were tuned by varying the stirring rate. Remarkable negative contrast was observed because USPIO nanoparticles (13.1?+/-?2.1?nm) generated high transversal relaxivity r2 (188?+/-?3?m m-1?s-1) and saturation magnetization (94?emu?g-1 Fe). The USPIO nanoparticles were coated with PDA [2-(pyridyldithio)-ethylamine; PDA nanoparticles] containing functional polymer, which can be readily synthesized by Michael addition. The PDA nanoparticles were conjugated with RGD peptide (RGD nanoparticles) for targeting the specific site. The target specificity and high relaxivity allowed RGD nanoparticles to differentiate the expression level of integrin receptor on several cell lines and tumors (MCF-7, A-549, HT-29 and HT-1080) by in vitro and in vivo MR imaging. Importantly, a remarkable negative contrast (-51.3?+/-?6.7%) was observed for in vivo MR imaging of MCF-7 tumor. This result implies that the RGD nanoparticles that greatly enhance the MR imaging are highly sensitive for early stage tumor detection. Copyright (c) 2012 John Wiley & Sons, Ltd.