- Synthesis, photophysical, electrochemical, tumor-imaging, and phototherapeutic properties of purpurinimide-N-substituted cyanine dyes joined with variable lengths of linkers
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Purpurinimide methyl esters, bearing variable lengths of N-substitutions, were conjugated individually to a cyanine dye with a carboxylic acid functionality. The results obtained from in vitro and in vivo studies showed a significant impact of the linkers
- Williams, Michael P. A.,Ethirajan, Manivannan,Ohkubo, Kei,Chen, Ping,Pera, Paula,Morgan, Janet,White, William H.,Shibata, Masayuki,Fukuzumi, Shunichi,Kadish, Karl M.,Pandey, Ravindra K.
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- Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes
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This report presents a simple strategy to introduce various functionalities in a cyanine dye (bis-indole-N-butylsulfonate-polymethine bearing a fused cyclic chloro-cyclohexene ring structure), and assess the impact of these substitutions in tumor uptake, retention and imaging. The results obtained from the structural activity relationship (SAR) study demonstrate that certain structural features introduced in the cyanine dye moiety make a remarkable difference in tumor avidity. Among the compounds investigated, the symmetrical CDs containing an amino-phenyl thioether group attached to a cyclohexene ring system and the two N-butyl linkers with terminal sulfonate groups in benzoindole moieties exhibited excellent tumor imaging ability in BALB/c mice bearing Colon26 tumors. Compared to indocyanine green (ICG), approved by FDA as a blood pooling agent, which has also been investigated for the use in tumor imaging, the modified CD selected on the basis of SAR study produced enhanced uptake and longer retention in tumor(s). A facile approach reported herein for introducing a variety of functionalities in tumor-avid CD provides an opportunity to create multi-imaging modality agent(s). Using a combination of mass spectrometry and absorbance techniques, the photobleaching of one of the CDs was analyzed and significant regioselective photooxidation was observed.
- Patel, Nayan J.,Manivannan, Ethirajan,Joshi, Penny,Ohulchanskyy, Tymish J.,Nani, Roger R.,Schnermann, Martin J.,Pandey, Ravindra K.
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p. 1219 - 1230
(2015/09/15)
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- CYANINE DYE COMPOUND AND PREPARATION METHOD THEREFOR, AND DUAL-FUNCTION AGENT FOR PHOTODYNAMIC THERAPY AND PREPARATION METHOD THEREFOR
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Disclosed are a cyanine dye compound and a preparation method therefor, and a dual-function agent for photodynamic therapy and a preparation method therefor. The provided cyanine dye compound is connected to multiple markers, which improves the accuracy o
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- Regioselective synthesis and photophysical and electrochemical studies of 20-substituted cyanine dye-purpurinimide conjugates: Incorporation of Ni II into the conjugate enhances its tumor-uptake and fluorescence-imaging ability
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We report herein a simple and efficient approach to the synthesis of a variety of meso-substituted purpurinimides. The reaction of meso-substituted purpurinimide with N-bromosuccinimide regioselectively introduced a bromo functionality at the 20-position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso-substituted analogues. Interestingly, the free base and the metalated analogues showed remarkable differences in photosensitizing efficacy (PDT) and tumor-imaging ability. For example, the free-base conjugate showed significant in vitro PDT efficacy, but limited tumor avidity in mice bearing tumors, whereas the corresponding NiII derivative did not produce any cell kill, but showed excellent tumor-imaging ability at a dose of 0.3 μmol kg-1 at 24, 48, and 72 h post-injection. The limited PDT efficacy of the Ni II analogue could be due to its inability to produce singlet oxygen, a key cytotoxic agent required for cell kill in PDT. Based on electrochemical and spectroelectrochemical data in DMSO, the first one-electron oxidation (0.52 V vs. SCE) and the first one-electron reduction (-0.57-0.67 V vs. SCE) of both the free base and the corresponding NiII conjugates are centered on the cyanine dye, whereas the second one-electron reduction (-0.81 V vs. SCE) of the two conjugates is assigned to the purpurinimide part of the molecule. Reduction of the cyanine dye unit is facile and occurs prior to reduction of the purpurinimide group, which suggests that the cyanine dye unit as an oxidant could be the driving force for quenching of the excited triplet state of the molecules. An interaction between the cyanine dye and the purpurinimide group is clearly observed in the free-base conjugate, which compares with a negligible interaction between the two functional groups in the NiII conjugate. As a result, the larger HOMO-LUMO gap of the free-base conjugate and the corresponding smaller quenching constant is a reason to decrease the intramolecular quenching process and increase the production of singlet oxygen to some degree. Copyright
- Ethirajan, Manivannan,Chen, Ping,Ohulchanskyy, Tymish Y.,Goswami, Lalit N.,Gupta, Anurag,Srivatsan, Avinash,Dobhal, Mahabeer P.,Missert, Joseph R.,Prasad, Paras N.,Kadish, Karl M.,Pandey, Ravindra K.
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p. 6670 - 6684
(2013/07/05)
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