A sialic acid-targeted near-infrared theranostic for signal activation based intraoperative tumor ablation

Wu, Xuanjun; Yu, Mingzhu; Lin, Bijuan; Xing, Hongjie; Han, Jiahuai; Han, Shoufa

doi:10.1039/c4sc02248c

Cited by 68 publications

(50 citation statements)

References 42 publications

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“…Therefore, blocked sialic acid expression in tumor cells is most likely responsible for the observed effects in the tumor microenvironment, although diminished sialic acid expression on the local immune cells may contribute as well. In line with these findings, Wu and colleagues showed that tumor cells have a higher preference to take up sialic acids compared with other tissues (39,40). We found, however, also a difference in the sensitivity of B16-F10 cells and 9464D cells for Ac 5 3F ax Neu5Ac in vitro and in vivo.…”

Section: Discussionsupporting

confidence: 90%

Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

et al. 2018

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Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to the immunosuppressive microenvironment and tumor immune evasion. However, the mechanisms by which these sugars modulate antitumor immunity as well as therapeutic strategies directed against them are limited. Here we report that intratumoral injections with a sialic acid mimetic Ac3FNeu5Ac block tumor sialic acid expression and suppress tumor growth in multiple tumor models. Sialic acid blockade had a major impact on the immune cell composition of the tumor, enhancing tumor-infiltrating natural killer cell and CD8 T-cell numbers while reducing regulatory T-cell and myeloid regulatory cell numbers. Sialic acid blockade enhanced cytotoxic CD8 T-cell-mediated killing of tumor cells in part by facilitating antigen-specific T-cell-tumor cell clustering. Sialic acid blockade also synergized with adoptive transfer of tumor-specific CD8 T cells and enhanced CpG immune adjuvant therapy by increasing dendritic cell activation and subsequent CD8 T-cell responses. Collectively, these data emphasize the crucial role of sialic acids in tumor immune evasion and provide proof of concept that sialic acid blockade creates an immune-permissive tumor microenvironment for CD8 T-cell-mediated tumor immunity, either as single treatment or in combination with other immune-based intervention strategies. Sialic acid sugars function as important modulators of the immunosuppressive tumor microenvironment that limit potent antitumor immunity. http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg .

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Section: Discussionsupporting

confidence: 90%

Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

et al. 2018

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“…Figure 1A shows Sia−pNIR is responsive to acidic pH with optimal turn-on fluorescence within pH 4.0−5.5, which is consistent as previously reported. 35 Analogous to Sia−pNIR, Glu−pNIR is nearly nonfluorescent at alkaline conditions and displays enhanced fluorescence emission centered at 740 nm as the buffer pH decreases ( Figure 1B), confirming acidic pH-mediated fluorogenic opening of the intramolecular ring of the pNIR domain (Scheme 1). Maximal fluorescence observed in pH 4.0−5.5 overlaps physiological lysosomal acidity window.…”

Section: ■ Results and Discussionmentioning

confidence: 89%

“…These results show the use of Sia− pNIR for activatable and targetable inflammation imaging and also the potentials of altered lysosome acidity in host cells undergoing inflammation as a new biomarker for inflammation diagnosis. 35 LysoTracker green DND-26 was purchased from Invitrogen. All other chemicals were used as received from Alfa Aesar.…”

Section: ■ Conclusionmentioning

confidence: 99%

Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore

Lin

et al. 2015

Anal. Chem.

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Inflammation causes significant morbidity and mortality, necessitating effective in vivo imaging of inflammation. Prior approaches often rely on combination of optical agents with entities specific for proteinaceous biomarkers overexpressed in inflammatory tissues. We herein report a fundamentally new approach to image inflammation by targeting lysosomes undergoing acidification in inflammatory cells with a sialic acid (Sia) conjugated near-infrared profluorophore (pNIR). Sia-pNIR contains a sialic acid domain for in vivo targeting of inflamed tissues and a pNIR domain which isomerizes into fluorescent and optoacoustic species in acidic lysosomes. Sia-pNIR displays high inflammation-to-healthy tissue signal contrasts in mice treated with Escherichia coli, Staphylococcus aureus, or lipopolysaccharide. In addition, inflammation-associated fluorescence is switched off upon antibiotics treatment in mice. This report shows the potentials of Sia-pNIR for activatable dual-modality inflammation imaging, and particularly the use of lysosomes of inflamed cells as a previously unappreciated biomarker for inflammation imaging.

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“…They likely can be used for photothermal therapy and controlled release in disease states that have tissue acidosis. 10 In addition, they can also be utilized for another important application, namely, ratiometric photoacoustic imaging of acidic pH.…”

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confidence: 99%

Croconaine rotaxane for acid activated photothermal heating and ratiometric photoacoustic imaging of acidic pH

et al. 2016

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A sialic acid-targeted near-infrared theranostic for signal activation based intraoperative tumor ablation

Abstract: A sialic acid-targeted near-infrared profluorophore with pH-responsive fluorescence and photothermal properties was developed for fluorescence-guided staging and photothermal therapy of viable tumors exposed during surgery.

Cited by 68 publications

References 42 publications

Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

Lysosomal pH Decrease in Inflammatory Cells Used To Enable Activatable Imaging of Inflammation with a Sialic Acid Conjugated Profluorophore

Croconaine rotaxane for acid activated photothermal heating and ratiometric photoacoustic imaging of acidic pH

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