Intracellular Proteolytic Disassembly of Self-Quenched Near-Infrared Nanoparticles Turning Fluorescence on for Tumor-Targeted Imaging

Jiang, Jinhui; Zhao, Zhibin; Hai, Zijuan; Wang, Hongyong; Liang, Gaolin

doi:10.1021/acs.analchem.7b02971

Cited by 26 publications

(17 citation statements)

References 25 publications

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“…, NIR-CBT-Cleaved-NP ) had a decreased diameter of 131.7 ± 21.5 nm but did not disappear (Figure 3D). This was because the CES-cleavable ester bonds are located at the side chains on the particle surface, but not at the skeletons of the nanoparticle as we previously did 23-24. Similar to the results of CES cleavage, the incubation of NIR-CBT-NP in CES-overexpressing HepG2 cell lysate at 37 °C for 4 h also induced the detachment of Cy5.5 from the nanoparticle to turn the fluorescence “On” by 74-fold (Figures S14-S15).…”

Section: Resultsmentioning

confidence: 85%

“…Moreover, their longer retention time in cells and tumor regions further enhance their imaging performance 21-22. Recently, Liang and coworkers reported two NIR fluorescence nanoprobes which could be cleaved by tumor-overexpressing enzymes to turn “On” the fluorescence and employed them for tumor imaging 23-24. However, the enzyme cleavage sites of these two nanoprobes are located on the skeletons (not the side chains) of the nanoparticles (NPs), leading to relatively low enzymatic cleavage efficiency.…”

Section: Introductionmentioning

confidence: 99%

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Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging

Chen¹,

Kuang²,

Zheng³

et al. 2019

Theranostics

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Near-infrared (NIR) nanoprobes with fluorescence “Turn-On” property are advantageous in cancer diagnosis but, to the best of our knowledge, “smart” nanoprobe that simultaneously targets both biotin receptor and carboxylesterase (CES) for HepG2 tumor-dual targeted imaging has not been reported.Methods: Using CBT-Cys click condensation reaction, we rationally designed a “smart” NIR fluorescence probe H2N-Cys(StBu)-Lys(Biotin)-Ser(Cy5.5)-CBT (NIR-CBT) and used it to facilely prepare the fluorescence-quenched nanoparticle NIR-CBT-NP.Results: In vitro results indicated that, after NIR-CBT-NP was incubated with CES for 6 h, its fluorescence was turned “On” by 69 folds. Cell experiments verified that NIR-CBT-NP was uptaken by HepG2 cells via biotin receptor-assisted endocytosis and its fluorescence was turned “On” by intracellular CES hydrolysis. Moreover, NIR-CBT-NP was successfully applied to image both biotin receptor- and CES-overexpressing HepG2 tumors.Conclusion: Fluorescence-quenched nanoparticle NIR-CBT-NP was facilely prepared to actively target biotin receptor-overexpressing HepG2 cancer cells and turn the fluorescence “On” by intracellular CES hydrolysis for tumor-dual targeted imaging. We anticipate that our fluorescence “Turn-On” nanoparticle could be applied for liver cancer diagnosis in clinic in the near future.

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Section: Resultsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging

Chen¹,

Kuang²,

Zheng³

et al. 2019

Theranostics

Self Cite

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“…Considering the inherent sensitivity of fluorescence lifetime to aggregation, this triggered aggregation system may serve as a means of producing contrast in the lifetime of a covalently-linked fluorescent reporter. This scaffold could then be caged by substrates or other moieties to facilitate smart imaging in response to enzymes or cellular conditions of interest, a strategy thoroughly demonstrated by previous work 20, 25–33, 35–38 . For instance, it is reported that many cancer cell lines produce increased levels of glutathione (GSH) compared to their normal tissue counterparts 39–41 ; caging the sulfhydryl group of the scaffold with a reduction-sensitive disulfide bond would facilitate glutathione-responsive lifetime imaging (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…This reaction is rapid 24 (with a second-order rate constant of 9.19 M −1 s -1 ) and can be controlled by caging portions of the 1,2-aminothiol group to create a bio-responsive aggregation system 23 . This system has been used as a platform for a wide variety of imaging methods 25–34 , including steady-state fluorescence imaging 20, 35–38 , but it has not been examined as a platform for time-resolved fluorescence imaging.…”

Section: Introductionmentioning

confidence: 99%

Responsive fluorophore aggregation provides spectral contrast for fluorescence lifetime imaging

Schleyer

Datko²,

Burnside³

et al. 2020

Preprint

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Fluorophores experience altered emission lifetimes when incorporated into and liberated from macromolecules or molecular aggregates; this trend suggests the potential for a fluorescent, responsive probe capable of undergoing self-assembly and aggregation and consequently altering the lifetime of its fluorescent moiety to provide contrast between the active and inactive probes. We developed a cyanobenzothioazole-fluorescein conjugate (1), and spectroscopically examined the lifetime changes caused by its reduction-induced aggregation in vitro. A decrease in lifetime was observed for compound 1 in a buffered system activated using the biological reducing agent glutathione, suggesting a possible approach for designing responsive self-aggregating lifetime imaging probes.

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“…As such, the multi-vitamin transporter is generally overexpressed in many cancer cells ( e.g. lung, colon, ovarian, breast and gastric cancer) 31, 32, providing theoretical basis for biotin-tagged probes which shows high affinity to tumor cells 33-35. Additionally, the stimuli-dependent strategy for imaging probe can allow the probe to be selectively released only in the presence of the specific environment, such as reactive oxygen species (ROS) 36, enzymes 37-39, pH value 40 etc.…”

Section: Introductionmentioning

confidence: 99%

GSH Activated Biotin-tagged Near-Infrared Probe for Efficient Cancer Imaging

Guo¹,

Huang²,

Zhang³

et al. 2019

Theranostics

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Tumor imaging tools with high specificity and sensitivity are needed to aid the boundary recognition in solid tumor diagnosis and surgical resection. In this study, we developed a near infra-red (NIR) probe ( P6 ) for in vitro/in vivo tumor imaging on the basis of the dual strategy of cancer cell targeting and stimulus-dependent activation. The selective imaging capacity towards cancer cells of P6 was thoroughly investigated, and the potential mechanisms of endocytosis were preliminary explored. Methods: GSH-activated biotin labelled NIR probe ( P6 ) was designed, synthesized and characterized. The GSH responsive properties were systematically illustrated through UV-vis, fluorescent tests and LC-MS analysis. In vitro fluorescent imaging of probe P6 was collected in various living cancer cell lines ( i.e. SW480, HGC-27, H460, BxPC-3, KHOS) and normal cell lines ( i.e. BEAS-2B, HLF-1, THP1) under confocal laser scanning microscopy. Probe P6 was further applied to image primary human cancer cells which were freshly isolated from the peritoneal carcinoma and rectal cancer patients. Serial sections of human tumor tissues were collected and sent for H&E (hematoxylin-eosin) staining and P6 imaging. Live fluorescent and photoacoustic imaging were used to investigate the in vivo imaging of P6 in both tumor and normal tissues in HGC-27 and KHOS xenograft model. Results: Probe P6 could be recognized and transported into cancer cells by tumor specific biotin receptors and efficiently be triggered by GSH to release fluorophore 4 . In fact, the cellular uptake of P6 could be partially blocked by the addition of free biotin. Furthermore, probe P6 could image various cancer cell lines, as well as primary cancer cells, exhibiting a ten-fold increase in fluorescence intensity over normal cells. In freshly dissected cancer tissues, P6 fluorescent imaging distinguished the cancerous area under confocal laser scanning microscopy, which was exact the same area as indicated by H&E staining. We also found that P6 exhibited superior selectivity against cancer tissues by local injection. Conclusion: In this study, we developed a dual-modal NIR probe P6 with enhanced cellular uptake into cancer cells and environmental stimulus triggered fluorescence. Our strategy provided a novel insight into the development of imaging tools that could be potentially used for fluorescent image-guided cancer boundary recognition and possibly cancer diagnosis.

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Intracellular Proteolytic Disassembly of Self-Quenched Near-Infrared Nanoparticles Turning Fluorescence on for Tumor-Targeted Imaging

Cited by 26 publications

References 25 publications

Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging

Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging

Responsive fluorophore aggregation provides spectral contrast for fluorescence lifetime imaging

GSH Activated Biotin-tagged Near-Infrared Probe for Efficient Cancer Imaging

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