Fluorescent Carbonaceous Nanodots for Noninvasive Glioma Imaging after Angiopep-2 Decoration

Ruan, Shaobo; Qian, Jun; Shen, Shun; Chen, Jiantao; Zhu, Jiaan; Jiang, Xinguo; He, Qin; Yang, Wu; Gao, Huile

doi:10.1021/bc500474p

Cited by 48 publications

(27 citation statements)

References 41 publications

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“…The particle size of the CDs was 4.9 nm, and the size increased to 8.3 nm after PEGylation (Figure 1), which was consistent with our previous studies [24,25] . According to TEM, the CDs were all spherical and were well dispersed with an average size of 3-4 nm ( Figure 1C); in comparison, the TEM size of PEG-CDs was similar to that of the CDs, which was consistent with results from our previous study [26] .…”

Section: Characterization Of Cds and Peg-cdssupporting

confidence: 91%

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

et al. 2015

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Aim: Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models. Methods: Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg -1 ·d -1 ) or PEG-CDs (size: 8.3 nm, 5 mg·kg -1 ·d -1 ) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf. Results: Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments. Conclusion: CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.

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Section: Characterization Of Cds and Peg-cdssupporting

confidence: 91%

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

et al. 2015

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“…In vivo results demonstrated that CNP could target the heart, in which the fluorescent intensity was much higher than that in other organs, even liver, and spleen. Furthermore, Green emissive CDs prepared from glucose and glutamic acid by the pyrolysis route [104]. Angiopep-2 is one such ligand whose receptor is low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed in glioma cells [105].…”

Section: Fluorescent Cds Conjugated With Targeting Unitmentioning

confidence: 99%

Recent advance of carbon dots in bio-related applications

Wang

Bao

et al. 2020

J. Phys. Mater.

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Carbon dots (CDs) is a kind of carbon nanoparticles with a plentiful of surface functional groups and tunable emission with different excitation wavelength. Broadly speaking, CDs include carbon nanodots, carbon quantum dots, graphene quantum dots, carbonized polymer dots. Due to the unique nature, they are explored for various applications in the bio-related fields such as bioimaging, sensor for ion and (bio)molecules, catalyst, LED and other fields. They are viewed as great alternative tracers to the current fluorescent biomarkers in personalized nanomedicine and surgery operation monitoring. In this review, we summarized the recent progress in the development of CDs, including improvement in fluorescence properties, two-photon fluorescence, and integration with other modalities as theragnostic agents. Specifically, we discussed the preparation of dual-modal imaging agents to improve the accuracy of diagnosis, the combination of imaging and targeting functionality for the effective accumulation of biomarkers, and the integration of imaging and therapeutic agents to effectively monitor the localization and concentration of therapeutic agents. Finally, the theragnostic agents composed of three functionalities (e.g. targeting, imaging, and therapy) were summarized to provide readers with future perspectives in this field.

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“…Another Angiopep-2 targeting agent, with Angiopep-2 anchored to carbonaceous nanoparticles, allows for NIR imaging and preferential targeting of orthotopic C6 glioma models, with a TNR of 1.73. 69 Angiopep-2 has been linked to gadolinium for use with preoperative MRI and surgical planning, 67 and to chemotherapeutic and phototherapeutic agents for brain tumor treatment. 70-73 A combination of Angiopep-2 targeting with activating cell penetrating peptide (ACP) and the chemotherapeutic agent docetaxel generated a more potent chemotherapeutic than without the ACP fragment in a mouse orthotopic glioma model.…”

Section: Targeted Fluorescent Molecular Imaging Agentsmentioning

confidence: 99%

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

et al. 2016

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The median life expectancy following a diagnosis of glioblastoma (GBM) is 15 months. While chemotherapeutics may someday cure GBM by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy – thereby highlighting where to resect, and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult to observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus non-tumor tissue. In this review, we briefly summarize non-targeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each.

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Fluorescent Carbonaceous Nanodots for Noninvasive Glioma Imaging after Angiopep-2 Decoration

Cited by 48 publications

References 41 publications

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Recent advance of carbon dots in bio-related applications

Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review

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