Computational study of photosensitizing IR 780 and its interaction with transition metals cations
Heptamethine dyes have being explored in photodynamic therapy (PDT)[1], since they are reported to have photosensitizing characteristics. Besides, experimental results indicated that its interaction with magnetic nanoparticles influenced their thermal and spectroscopic properties. have studied the electronic and thermal properties of IR780 molecule (Figure 1), a lipophilic agent, using Density Functional Theory (DFT) simulations. DFT calculations were performed using B3LYP functional and D3BJ empirical dispersion correction, considering 6-31G(d,p) basis set and def2 Orca software. Also, excited state optimization using time methodology was performed in order to compare the infrared spectra in both cases. In order to understand the role of the interaction with nanoparticles, molecule's bond with transition metals cations Mn the changes in dipole moment magnitude and direction, also changes in charge distribution. Comparing IR780 in ground and excited states, dipole moment decreased subs and its direction also changes. In terms of charge distribution the largest differences were in atoms of the central ring. Considering the structures with cations, the larger charge distribution variations were observed in atoms nearer from the expected. Differences in single point energies of IR780 bonded to metal cations indicate formation of chemical bonds, and the difference increases proportionally with atomic radii. Although it was not observed significant change in the molecul ground and excited states, changes in the infrared spectrum were noticed. In order to clarify these results, further studies are in progress. b , Ronei Miotto, Paula Homem – Santo André – Brazil – Goiânia – Brazil are chemical compounds within the indocyanine dye family, and -TZVP auxiliary basis, as implemented in -dependent DFT (TD , Fe and Co were investigated, aiming to analyze e's geometry between -de-Mello
A NIR heptamethine dye with intrinsic cancer targeting, imaging and photosensitizing properties.
The future personalized oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging, and cytotoxic activities. In our recent study, we have recently identified a near infrared fluorescent heptamethine dye, IR-780, with unexpected preferential accumulation in a broad spectra of tumor cells for in vivo tumor targeting and imaging. On the basis of this foregoing work, in this study, we describe here the chemical synthesis and biological characterization of an analog of IR-780, termed as IR-808, which not only possesses similar tumor targeting and imaging properties of IR-780, but also has unique photodependent cytotoxic activity. In addition, IR-808 also exhibits favorable optical and pharmacokinetic properties, as well as good biocompatibility. This dye may hold promise as a candidate multifunctional theranostic agent for future tumor targeted imaging and photodynamic therapy.
Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging.
With the emerging concept of individualized cancer therapy, it becomes crucial to develop methods for the noninvasive assessment of treatment outcome. With this in mind, we designed a novel approach for the comprehensive evaluation of response to chemotherapy with the established agent doxorubicin in a preclinical breast cancer model. This approach delivers information not only about change in tumor size but also about target antigen expression. Our strategy relies on a tumor-specific contrast agent (MN-EPPT) targeting the underglycosylated MUC-1 (uMUC-1) tumor antigen, found on more than 90% of breast cancers and predictive of chemotherapeutic response. MN-EPPT consists of superparamagnetic iron oxide nanoparticles (MN) for magnetic resonance imaging, modified with Cy5.5 dye (for near-IR fluorescence optical imaging), and conjugated to peptides (EPPT), specifically recognizing uMUC-1. In vivo, treatment of mice bearing orthotopic human breast carcinomas with doxorubicin led to a reduction in tumor mass and resulted in down-regulation of uMUC-1. The tumor-specific accumulation of MN-EPPT allowed the assessment of change in tumor volume by noninvasive imaging. Furthermore, in mice injected with MN-EPPT, tumor delta-T2 was significantly reduced after treatment with doxorubicin, indicating a lower accumulation of MN-EPPT and reflecting the reduced expression of uMUC-1. With these studies, we have shown the utility of magnetic resonance imaging for the multiparametric characterization of breast tumor response to chemotherapy. This approach has the potential of significantly advancing our ability to better direct the development of molecularly targeted individualized therapy protocols because it permits the monitoring of therapy on a molecular scale.