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IR-783, a commercially available near-infrared (NIR) heptamethine cyanine dye, has been used for selective tumor imaging in breast, prostate, cervical, and brain cancers in vitro and in vivo. Although the molecular mechanism behind the structure-inherent tumor targeting of IR-783 has not been well-demonstrated, IR-783 has unique properties such as a good water solubility and low cytotoxicity compared with other commercial heptamethine cyanine dyes. The goal of this study is to evaluate the phototherapeutic efficacy of IR-783 as a tumor-targeted photothermal agent in human colorectal cancer xenografts. The results demonstrate that IR-783 shows both the subcellular localization in HT-29 cancer cells and preferential accumulation in HT-29 xenografted tumors 24 h after its intravenous administration. Furthermore, the IR-783 dye reveals the superior capability to convert NIR light into heat energy under 808 nm NIR laser irradiation in vitro and in vivo, thereby inducing cancer cell death. Taken together, these findings suggest that water-soluble anionic IR-783 can be used as a bifunctional phototherapeutic agent for the targeted imaging and photothermal therapy (PTT) of colorectal cancer. Therefore, this work provides a simple and effective approach to develop biocompatible, hydrophilic, and tumor-targetable PTT agents for targeted cancer phototherapy.

IR-783, a near-infrared heptamethine cyanine dye, has been reported to possess cancer targeting and anticancer effects; However, the molecular mechanism by which IR-783 exhibits anti-breast cancer activity is unclear. In the present study, the inhibitory effects of IR-783 on the proliferation and migration of breast cancer cells were investigated. Our results revealed that IR-783 inhibited MDA-MB-231 and MCF-7 cell proliferation in a dose- and time-dependent manner by inducing cell cycle arrest at the G0/G1 phase. In addition, a Transwell assay demonstrated that IR-783 treatment suppressed the migratory ability of MDA-MB-231 and MCF-7 cells. Furthermore, IR-783 treatment decreased the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 in MDA-MB-231 cells. Furthermore, IR-783 induced MDA-MB-231 and MCF-7 cell mitochondrial fission, and also decreased the levels of ATP. This was accompanied with a decrease in polymerized filamentous actin, which is the fundamental component of filopodia at the cell surface. Collectively, the results of the present study demonstrated that IR-783 inhibited the proliferation and migration of MDA-MB-231 and MCF-7 cells by inducing mitochondrial fission and subsequently decreasing ATP levels, resulting in cell cycle arrest and filopodia formation suppression. These findings suggest that IR-783 may be developed into an effective novel drug for treating breast cancer.

IR‐783 is a kind of heptamethine cyanine dye that exhibits imaging, cancer targeting and anticancer properties. A previous study reported that its imaging and targeting properties were related to mitochondria. However, the molecular mechanism behind the anticancer activity of IR‐783 has not been well demonstrated. In this study, we showed that IR‐783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA‐MB‐231 cells to IR‐783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR‐783 induced dynamin‐related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission‐1 (Fis1), and decreased the expression of mitochondrial fusion proteins mitofusin1 (Mfn1) and optic atrophy 1 (OPA1). Moreover, knockdown of Drp1 markedly blocked IR‐783‐mediated mitochondrial fission, loss of MMP, ATP depletion, mPTP opening and apoptosis. Our in vivo study confirmed that IR‐783 markedly inhibited tumour growth and induced apoptosis in an MDA‐MB‐231 xenograft model in association with the mitochondrial translocation of Drp1. Taken together, these findings suggest that IR‐783 induces apoptosis in human breast cancer cells by increasing Drp1‐mediated mitochondrial fission. Our study uncovered the molecular mechanism of the anti‐breast cancer effects of IR‐783 and provided novel perspectives for the application of IR‐783 in the treatment of breast cancer.

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, a heptamethine cyanine (HMC) dye, impedes the proliferation of breast cancer cells, even without light. Although studies have investigated the efficacy of IR-783 in cell and animal studies, its efficacy in clinical settings remains unknown. Therefore, we aimed to determine the efficacy of PDT using IR-783 liposomes. An HMC dye, excited by long-wavelength infrared light and with high tissue permeability, was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with either tongue or breast cancer, one each. IR-783 liposomes inhibited cell proliferation in tongue cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor but also to the improvement in airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers.

The multidrug resistance protein 1 (MDR1; P-glycoprotein) has been associated with efflux of chemotherapeutic agents from tumor cells and with poor patient prognosis. This study evaluated the feasibility of non-invasive, non-radioactive near infrared (NIR) imaging methodology for detection of MDR1 functional activity in tumors. Initial accumulation assays were conducted in MDR1-overexpressing MDCK cells (MDCK-MDR1) and control MDCK cells (MDCK-CT) using the NIR dyes indocyanine green (ICG), IR-783, IR-775, rhodamine 800, XenoLight DiR, and Genhance 750, at 0.4 μM-100 μM. ICG and IR-783 were also evaluated in HT-29 cells in which MDR1 overexpression was induced by colchicine (HT-29-MDR1) and their controls (HT-29-CT). optical imaging studies were conducted using immunodeficient mice bearing HT-29-CT and HT-29-MDR1 xenografts. ICG's emission intensity was 2.0- and 2.2-fold higher in control versus MDR1-overexpressing cells, in MDCK and HT-29 cell lines, respectively. The respective IR-783 control:MDR1 ratio was 1.4 in both MDCK and HT-29 cells. Optical imaging of mice bearing HT-29-CT and HT-29-MDR1 xenografts revealed a statistically non-significant, 1.7-fold difference ( > 0.05) in ICG emission intensity between control and MDR1 tumors. No such differences were observed with IR-783. ICG and IR-783 appear to be weak MDR1 substrates. , low sensitivity and high between-subject variability impair the ability to use the currently studied probes as markers of tumor MDR1 activity. The results suggest that, for future use of this technology, additional NIR probes should be screened as MDR1 substrates.