Substituent Effects on the Assembly of Helical Cyanine Dye Aggregates in the Minor Groove of a DNA Template

Stadler, Andreas; Renikuntla, Babu Rao; Yaron, David; Fang, Adam; Armitage, Bruce A.

doi:10.1021/la104329c

Cited by 29 publications

(47 citation statements)

References 23 publications

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“…DZ‐CIS NIR signals were detected at least 7 days after a single administration, like our prototype IR783 and MHI‐148 analogs . DZ‐CIS is prevented from diffusing out from cancer cells by interaction with cellular nucleic acids and proteins …”

Section: Resultsmentioning

confidence: 87%

“…18,21-23,31 DZ-CIS is prevented from diffusing out from cancer cells by interaction with cellular nucleic acids and proteins. 37,38 After whole body NIR imaging, mice were euthanized at 24 hours and necropsy specimens were again imaged by NIR. Higher NIR signals were detected in xenograft tumors than host tissues (Fig.…”

Section: Dz-cis Accumulates In Burkitt Lymphoma Cells and Tumorsmentioning

confidence: 99%

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Targeting Burkitt lymphoma with a tumor cell–specific heptamethine carbocyanine‐cisplatin conjugate

Mrđenović

Zhang

Wang

et al. 2019

Cancer

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Background Burkitt lymphoma is a fast‐growing mature B cell malignancy, whose genetic hallmark is translocation and activation of the c‐myc gene. Prompt multiagent immunochemotherapy regimens can have favorable outcomes, but prognosis is poor in refractory or relapsed disease. We previously identified a novel family of near‐infrared heptamethine carbocyanine fluorescent dyes (HMCD or DZ) with tumor‐homing properties via organic anion‐transporting peptides. These membrane carriers have uptake in tumor cells but not normal cells in cell culture, mouse and dog tumor models, patient‐derived xenografts, and perfused kidney cancers in human patients. Methods Here we report the cytotoxic effects of a synthesized conjugate of DZ with cisplatin (CIS) on B cell lymphoma CA46, Daudi, Namalwa, Raji, and Ramos cell lines in cell culture and in xenograft tumor formation. Impaired mitochondrial membrane permeability was examined as the mechanism of DZ‐CIS–induced lymphoma cell death. Results The new conjugate, DZ‐CIS, is cytotoxic against Burkitt lymphoma cell lines and tumor models. DZ‐CIS retains tumor‐homing properties to mitochondrial and lysosomal compartments, does not accumulate in normal cells and tissues, and has no nephrotoxicity in mice. DZ‐CIS accumulated in Burkitt lymphoma cells and tumors induces apoptosis and retards tumor cell growth in culture and xenograft tumor growth in mice. Conclusion DZ‐CIS downregulated c‐myc and overcame CIS resistance in myc ‐driven TP53‐mutated aggressive B cell Burkitt lymphoma. We propose that DZ‐CIS could be used to treat relapsed/refractory aggressive Burkitt lymphomas.

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Section: Resultsmentioning

confidence: 87%

Section: Dz-cis Accumulates In Burkitt Lymphoma Cells and Tumorsmentioning

confidence: 99%

Targeting Burkitt lymphoma with a tumor cell–specific heptamethine carbocyanine‐cisplatin conjugate

Mrđenović

Zhang

Wang

et al. 2019

Cancer

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“…Carbocyanine dyes are bound by proteins and nucleic acids. 6, 7 It is possible that the binding to these macromolecules causes the retention. This unique feature of carbocyanine dye staining will facilitate the noninvasive detection of tumors with a high signal/noise ratio.…”

Section: Discussionmentioning

confidence: 99%

“…Inside tumor cells these dyes are bound by proteins or nucleic acids. 6, 7 Binding leads to fluorophore rigidization, causing a marked increase of extinction coefficient favoring NIR detection. 8-10 We previously defined two heptamethine carbocyanine dyes, IR-783 and its synthetic analog MHI-148, that display tumor cell specificity, being taken up and retained by human cancer but not non-cancerous cells due to the differential expression of organic anion transporting peptides (OATPs) in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Optical Imaging of Kidney Cancer with Novel Near Infrared Heptamethine Carbocyanine Fluorescent Dyes

et al. 2013

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PURPOSE To assess the application of near-infrared (NIR) heptamethine carbocyanine dyes, IR-783 and the synthetic analog MHI-148, as optical imaging agents for rapid detection of human kidney cancer. MATERIALS AND METHODS The uptake, retention and subcellular localization of these organic dyes were investigated in cultured kidney cancer cells. Tumor specificity of dye uptake and retention was evaluated by whole-body imaging of mice bearing human kidney cancer xenografts or freshly harvested clinical kidney cancer specimens. In addition, dye accumulation at the tissue and cellular levels was confirmed by ex vivo studies with results confirmed by fluorescence imaging of the frozen tissue sections. Peripheral blood spiked with kidney cancer cells was stained to simulate the detection of circulating tumor cells. RESULTS Preferential uptake and retention of carbocyanine NIR dyes was observed in cultured human kidney cancer cells, human kidney cancer cell-spiked whole blood, human kidney cancer xenografts and freshly harvested human kidney cancer tissues compared to normal kidney epithelial cells or normal host organs. CONCLUSIONS We described a new class of NIR heptamethine carbocyanine dyes showing potential for detecting kidney cancer cells in circulating blood and kidney cancer cells in clinical specimens. NIR carbocyanine dyes can be further developed as dual modality agents for deep-tissue imaging of localized and disseminated kidney cancer in patients.

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“…Studies have shown that the addition of substituents can alter the permanent molecular dipole moments and aggregation properties of molecules [25][26][27][28]. Misawa et al measured large changes in the static dipole moments of pseudoisocyanine bromide (PIC-Br) upon J-aggregation, revealing that cyanine molecules had the ability to achieve large static dipole moments [25].…”

Section: Introductionmentioning

confidence: 99%

Substituent Effects on the Solubility and Electronic Properties of the Cyanine Dye Cy5: Density Functional and Time-Dependent Density Functional Theory Calculations

et al. 2021

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The aggregation ability and exciton dynamics of dyes are largely affected by properties of the dye monomers. To facilitate aggregation and improve excitonic function, dyes can be engineered with substituents to exhibit optimal key properties, such as hydrophobicity, static dipole moment differences, and transition dipole moments. To determine how electron donating (D) and electron withdrawing (W) substituents impact the solvation, static dipole moments, and transition dipole moments of the pentamethine indocyanine dye Cy5, density functional theory (DFT) and time-dependent (TD-) DFT calculations were performed. The inclusion of substituents had large effects on the solvation energy of Cy5, with pairs of withdrawing substituents (W-W pairs) exhibiting the most negative solvation energies, suggesting dyes with W-W pairs are more soluble than others. With respect to pristine Cy5, the transition dipole moment was relatively unaffected upon substitution while numerous W-W pairs and pairs of donating and withdrawing substituents (D-W pairs) enhanced the static dipole difference. The increase in static dipole difference was correlated with an increase in the magnitude of the sum of the Hammett constants of the substituents on the dye. The results of this study provide insight into how specific substituents affect Cy5 monomers and which pairs can be used to engineer dyes with desired properties.

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Substituent Effects on the Assembly of Helical Cyanine Dye Aggregates in the Minor Groove of a DNA Template

Cited by 29 publications

References 23 publications

Targeting Burkitt lymphoma with a tumor cell–specific heptamethine carbocyanine‐cisplatin conjugate

Targeting Burkitt lymphoma with a tumor cell–specific heptamethine carbocyanine‐cisplatin conjugate

Optical Imaging of Kidney Cancer with Novel Near Infrared Heptamethine Carbocyanine Fluorescent Dyes

Substituent Effects on the Solubility and Electronic Properties of the Cyanine Dye Cy5: Density Functional and Time-Dependent Density Functional Theory Calculations

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