“…We observed strong overlapping signals of IR780-micelles and Mitotracker (Fig. 3b, merged), indicating a mitochondrial accumulation of IR780-micelles, which is consistent to previous reports that preferential accumulation of free IR780 dye and liposomal IR780 were found in mitochondria of multiple tumor cells [11, 12, 36]. Therefore, the incorporation of IR780 with liposomes or phospholipid micelles preserved the same mitochondrial retention feature as free IR780.Fig.…”
Section: Resultssupporting
confidence: 90%
“…Both dyes are approved for clinical use [9, 10]. Among other dyes, NIRF heptamethine cyanine dye IR780 was found to have excellent intrinsic tumor targeting and imaging properties without further modification [11–14], providing great potential for tumor NIRF imaging. IR780′s low cytotoxicity makes it of potential clinical use; however, it is also hydrophobic and insoluble in pharmaceutically acceptable solvents, thus an appropriate formulation is required for clinical use [15, 16].…”
BackgroundNear-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor.MethodsSelf-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation.ResultsThe loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 and 26 nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner.ConclusionThe IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1115-2) contains supplementary material, which is available to authorized users.
“…We observed strong overlapping signals of IR780-micelles and Mitotracker (Fig. 3b, merged), indicating a mitochondrial accumulation of IR780-micelles, which is consistent to previous reports that preferential accumulation of free IR780 dye and liposomal IR780 were found in mitochondria of multiple tumor cells [11, 12, 36]. Therefore, the incorporation of IR780 with liposomes or phospholipid micelles preserved the same mitochondrial retention feature as free IR780.Fig.…”
Section: Resultssupporting
confidence: 90%
“…Both dyes are approved for clinical use [9, 10]. Among other dyes, NIRF heptamethine cyanine dye IR780 was found to have excellent intrinsic tumor targeting and imaging properties without further modification [11–14], providing great potential for tumor NIRF imaging. IR780′s low cytotoxicity makes it of potential clinical use; however, it is also hydrophobic and insoluble in pharmaceutically acceptable solvents, thus an appropriate formulation is required for clinical use [15, 16].…”
BackgroundNear-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor.MethodsSelf-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation.ResultsThe loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 and 26 nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner.ConclusionThe IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1115-2) contains supplementary material, which is available to authorized users.
“…20 Under hypoxic conditions, active nuclear HIF1α protein interacts with a hypoxia response element (HRE) in the OATP promoter, resulting in increased transcription of OATP genes. By contrast, HIF1α is destabilized under normoxia due to rapid degradation initiated by the PHD/VHL pathway, 29 which is likely the mechanism responsible for the relatively low levels of OATPs generally observed in normal tissues. 93 Thus, inactivation of HIF1α∕OATPs signaling in normal cells and tissues blunts their sensitivity to recruit NIRF dyes for the long-lasting retention and preferential organelle-specific cellular localization seen in cancer cells.…”
Section: Tumor Hypoxia and Hif1α∕organicmentioning
confidence: 99%
“…72 Mechanistic study revealed that the mitochondrial accumulation of IR-780 increased the production of ROS and depolarization of mitochondrial membrane potential, leading to mitochondrial toxicity and cancer cell apoptosis without the need for any chemical conjugation. 29 Since the mitochondrial toxicity induced by these dyes was correlated with the increased length of alkyl chain, 73 Luo et al designed a series of IR-808 analogs, including IR-808DB, IR-808DH, and IR-808DCH, by increasing the length of the alkyl side chain as well as the lipophilicity of the IR-808 compound, and showed the higher antitumor effects of these analogs, such as IR-808DB, compared to cyclophosphamide in a series of tumor xenograft models. 17 …”
Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy," J. Biomed. Opt. 21(5), 050901 (2016), doi: 10.1117/1.JBO.21.5.050901. Abstract. A class of near-infrared fluorescence (NIRF) heptamethine cyanine dyes that are taken up and accumulated specifically in cancer cells without chemical conjugation have recently emerged as promising tools for tumor imaging and targeting. In addition to their fluorescence and nuclear imagingbased tumor-imaging properties, these dyes can be developed as drug carriers to safely deliver chemotherapy drugs to tumors. They can also be used as effective agents for photodynamic therapy with remarkable tumoricidal activity via photodependent cytotoxic activity. The preferential uptake of dyes into cancer but not normal cells is co-operatively mediated by the prevailing activation of a group of organic aniontransporting polypeptides on cancer cell membranes, as well as tumor hypoxia and increased mitochondrial membrane potential in cancer cells. Such mechanistic explorations have greatly advanced the current application and future development of NIRF dyes and their derivatives as anticancer theranostic agents. This review summarizes current knowledge and emerging advances in NIRF dyes, including molecular characterization, photophysical properties, multimodal development and uptake mechanisms, and their growing potential for preclinical and clinical use.
“…IR-780 iodide is a more recently developed NIR dye which is more stable than ICG. IR-780 is a lipophilic cationic heptamethine dye with higher fluorescence intensity than ICG192021. Currently, IR780 iodide has been reported to have the ability of producing singlet oxygen under irradiating at wavelength of 808 nm, which can be used for PDT22.…”
Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor-bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy.
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