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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.

Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the mechanistic properties of a specific group of NIR heptamethine carbocyanines including MHI-148 dye we identified and synthesized, and demonstrated these dyes to achieve cancer-specific imaging and targeting via a hypoxia-mediated mechanism. We found that cancer cells and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake in vitro and in vivo, which was directly mediated by hypoxia-inducible factor 1α (HIF1α). Microarray analysis and dye uptake assay further revealed a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) responsible for dye uptake, and the correlation between OATPs and HIF1α was manifested in progressive clinical cancer specimens. Finally, we demonstrated increased uptake of MHI-148 dye in situ in perfused clinical tumor samples with activated HIF1α/OATPs signaling. Our results establish these NIRF dyes as potential tumor hypoxia-dependent cancer-targeting agents and provide a mechanistic rationale for continued development of NIRF imaging agents for improved cancer detection, prognosis and therapy.

The effects of composition and metal particle size of platinum catalysts on ethane dehydrogenation were investigated on Pt x Sn 100Àx /Mg(Al)O (70 6 x 6 100) catalysts prepared with average particle sizes between $2 and 7 nm. At high conversions, catalyst deactivation from coke formation was a strong function of particle size and Sn/Pt. Deactivation decreased significantly with decreasing particle size and increasing Sn addition. To understand the true initial activity of un-deactivated catalysts, further experiments were run at low residence time conditions to limit ethene formation. For a fixed average particle size, ethane TOF and the selectivity to ethene increased with increasing content of Sn in the PtSn particle. For Pt and Pt 3 Sn compositions, ethane TOF increased with increasing particle size, while the selectivity to ethene was not strongly affected. The observed effects of particle size and composition are attributed to a combination of geometric and electronic factors.

Brain tumors and brain metastases are among the deadliest malignancies of all human cancers, largely due to the cellular blood-brain and blood-tumor barriers that limit the delivery of imaging and therapeutic agents from the systemic circulation to tumors. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. Here we identified and synthesized a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and derivative NIRF dye-drug conjugates for effective imaging and therapeutic targeting of brain tumors of either primary or metastatic origin in mice, which is mechanistically mediated by tumor hypoxia and organic aniontransporting polypeptide genes. We also demonstrate that these dyes, when conjugated to chemotherapeutic agents such as gemcitabine, significantly restricted the growth of both intracranial glioma xenografts and prostate tumor brain metastases and prolonged survival in mice. These results show promise in the application of NIRF dyes as novel theranostic agents for the detection and treatment of brain tumors.

Many presynaptic transcripts have been observed in axons, yet their role in synapse development remains unknown. Using visually and pharmacologically isolated presynaptic terminals from dissociated rat hippocampal neurons, we found that ribosomes and β-catenin mRNA preferentially localize to recently formed boutons. Locally translated β-catenin accumulates at presynaptic terminals where it regulates synaptic vesicle release dynamics. Thus, local translation of β-catenin is a newly described mechanism for axons to independently functionalize nerve terminals at great distances from cellular somata.

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Metastasis is a predominant cause of death for prostate cancer (PCa) patients; however, the underlying mechanisms are poorly understood. We report that monoamine oxidase A (MAOA) is a clinically and functionally important mediator of PCa bone and visceral metastases, activating paracrine Shh signaling in tumor-stromal interactions. MAOA provides tumor cell growth advantages in the bone microenvironment by stimulating interleukin-6 (IL6) release from osteoblasts, and triggers skeletal colonization by activating osteoclastogenesis through osteoblast production of RANKL and IL6. MAOA inhibitor treatment effectively reduces metastasis and prolongs mouse survival by disengaging the Shh-IL6-RANKL signaling network in stromal cells in the tumor microenvironment. These findings provide a rationale for targeting MAOA and its associated molecules to treat PCa metastasis.