Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor

Wu, Jason; Shi, Changhong; Chu, Gina Chia‐Yi; Xu, Qijin; Zhang, Yi; Li, Qinlong; Yu, John S.; Zhau, Haiyen E.; Chung, Lorinda

doi:10.1016/j.biomaterials.2015.07.028

Cited by 98 publications

(116 citation statements)

References 59 publications

(87 reference statements)

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“…NIRG treatment also significantly inhibited the growth of intracranial glioma and prostate tumor brain metastases, prolonging survival in mice. 25 These results demonstrate the great potential of these NIRF dyes and derived dye-drug conjugates for future development and application in the clinic as effective brain tumor theranostics.…”

Section: Brain Drug Deliverymentioning

confidence: 83%

“…Alternatively, genetic knockdown of HIF1α in cancer cells reduced the expression of select OATPs, such as OATP1B3 and OATP2B1, along with HIF1α-responsive genes, corresponding with reduced uptake of NIRF dye by cancer cells. 20,22 These mechanisms have been well demonstrated in prostate cancer and brain cancer so far, 20,22,25 and are expected to work in other cancers as well given the prevailing activation of tumor hypoxia and OATP expression in most types of cancers. 94,95 In addition, we have recently established a NIRF imaging method to analyze clinical tumor samples ex vivo, where the activation of HIF1α∕OATPs signaling could be recapitulated, evidenced by intense widespread nuclear HIF1α and cytoplasmic OATP1B3 protein expression in RCC samples but not adjacent normal tissues.…”

Section: Tumor Hypoxia and Hif1α∕organicmentioning

confidence: 99%

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Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

2016

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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.

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Section: Brain Drug Deliverymentioning

confidence: 83%

Section: Tumor Hypoxia and Hif1α∕organicmentioning

confidence: 99%

Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

2016

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“…The cancer cells used genitourinary cancers as representative model systems and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake leading to an increase of NIRF signals. This was directly mediated by hypoxia-inducible factor 1α (HIF1α) and a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) as shown by microarray analysis and dye uptake assay in situ in perfused clinical tumor samples [47]. …”

Section: Small Molecule and Dye Based Probesmentioning

confidence: 99%

Luminescent Probe Based Techniques for Hypoxia Imaging

Jaworski¹

2017

JNMR

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Hypoxia is a condition of tissue environments wherein a lower than normal level of oxygen is available, and it serves as the root cause and indicator of various diseases. Detection of hypoxia in tumors is imperative for furthering our understanding of the pathological effects and the development of proper treatments, as it is well established that hypoxic tumors are able to impede the cancer treatment process by being resistant to many therapies. It is important therefore to be able to detect hypoxia in tissues and tumors through in vivo imaging methods. A growing area for detection of hypoxia in vivo is the use of fluorescent/luminescent probes which has accelerated in recent years. The continued quest for improvements in selectivity and sensitivity has inspired researchers to pursue new strategies for fluorescence/luminescent probe design. This review will discuss various luminescent probes based on small molecules, dyes, macromolecules, and nanoparticles for sensitive and specific detection of oxygen levels directly or by indirect mechanisms such as the presence of enzymes or related factors that arise in a hypoxic environment. Following the particular mechanism of detection, each probe has specific structural and photophysical properties which permit its selectivity and sensitivity. These probes show promise in terms of low toxicity and high specificity among other merits discussed, and in providing new dimensions for hypoxia detection, these works contribute to future potential methods for clinical diagnosis of hypoxic tissues and tumors.

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“…Several recent studies have demonstrated the use of intraoperative fluorescent imaging as a tool to overcome some limitations of conventional white light surgery, to enhance the visual contrast between tumor and normal tissue [6–10]. Oral administration of 5-ALA induces PpIX fluorescence in high grade glioblastoma tumors, which can be imaged during fluorescent-guided surgery (FGS).…”

Section: Introductionmentioning

confidence: 99%

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

et al. 2016

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PurposeFluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level.ProcedureNude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3–4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1–48 h) and varying injection doses from 25 to 122 μg/kg (from human protein microdose equivalent to five times microdose levels).ResultsThe tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast.ConclusionThese results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions.

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Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and targeted drug delivery for human brain tumor

Cited by 98 publications

References 59 publications

Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

Luminescent Probe Based Techniques for Hypoxia Imaging

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

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