Influence of Surface Modifications on the Spatiotemporal Microdistribution of Quantum Dots In Vivo

Nekolla, Katharina; Kick, Kerstin; Sellner, Sabine; Mildner, Karina; Zahler, Stefan; Zeuschner, Dagmar; Krombach, Fritz; Rehberg, Markus

doi:10.1002/smll.201600071

Cited by 14 publications

(10 citation statements)

References 53 publications

(71 reference statements)

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“…Nevertheless, QDs with a CdSe core and a ZnS shell, coated with PEG, can not only greatly decrease the toxicity but also show little interaction with tissue constituents and bind to the target more efficiently. 17,43 In correspondence with other studies, we confirm that the QDs and QD-Apt was nontoxic and exhibited optimal biocompatibility. Moreover, studies have validated that the safe dose of QDs was 1 μM in vitro and 15 nM in vivo, which was higher than the concentrations used in this study.…”

Section: Discussionsupporting

confidence: 90%

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

Tang¹,

Huang²,

Zhang³

et al. 2017

IJN

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The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood–brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.

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Section: Discussionsupporting

confidence: 90%

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

Tang¹,

Huang²,

Zhang³

et al. 2017

IJN

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“…It has been reported that PEG coating not only greatly reduces toxicity, but also shows little interaction with tissue components (Nekolla et al, 2016). Tang et al utilized QDs with a positive, negative, or a PEG coating to study toxicity in a mouse model, and found that QDs coated with PEG resulted in fewer chronic injuries in vivo compared to the positive or negative QDs (Tang Y. et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Toxicity Evaluation of PEGylated CuInS2/ZnS Quantum Dots in BALB/c Mice

Zou

Chen

et al. 2019

Front. Pharmacol.

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In recent years, quantum dots (QDs) have emerged as a potential contrast agent for bioimaging due to their bright luminescence and excellent photostability. However, the wide use of QDs in vivo has been limited due to underlying toxicity caused by leakage of heavy metals. Although non-cadmium QDs have been developed to resolve this issue, a comprehensive understanding of the toxicity of these newly developed QDs remains elusive. In this study, we administered PEGylated copper indium sulfide/zinc sulfide (CuInS 2 /ZnS), which are typical non-cadmium QDs, and analyzed the long-term effects of these nanoparticles in BALB/c mice. Body weight, hematology, blood biochemistry, organ histology, and biodistribution were examined at different time points. We found no significant difference in body weight after injection of CuInS 2 /ZnS QDs. These CuInS 2 /ZnS QDs entered and were accumulated in major organs for 90 days post-injection. The majority of biochemical indicators were not significantly different between the QDs-treated group and the control group. In addition, no significant histopathological abnormalities were observed in the treated mice compared with the control mice. CuInS 2 /ZnS QDs did not lead to observable toxicity in vivo following either the administration of a high or low dose. Our research not only provides direct evidence of the bio-safety of CuInS 2 /ZnS QDs, but also a feasible method for evaluating nanoparticle toxicity.

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“…Consistently, a previous study showed no cytotoxicity of unfunctionalized CuInS/ZnS QDs in contrast to Cd-based QDs [ 35 ]. Despite the paucity of in vivo outcome, the major weakness of this study, the in vitro cytotoxicity data strongly advocate the in vivo safety of our QD-PCL scaffolds considering the small QD dose per scaffold, the slow in vivo degradation rate resulting in negligible amount of QD cleavages at a certain time-point, and the quick in vivo QD diffusion rate (<2 h) reported in literature [ 36 ].…”

Section: Discussionmentioning

confidence: 96%

Quantum dots-labeled polymeric scaffolds for in vivo tracking of degradation and tissue formation

Sim

Mir

Jelke

et al. 2022

Bioactive Materials

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Influence of Surface Modifications on the Spatiotemporal Microdistribution of Quantum Dots In Vivo

Cited by 14 publications

References 53 publications

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

In Vivo Toxicity Evaluation of PEGylated CuInS2/ZnS Quantum Dots in BALB/c Mice

Quantum dots-labeled polymeric scaffolds for in vivo tracking of degradation and tissue formation

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