Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood–brain barrier and targeted fluorescence imaging of glioma and tumor vasculature

Huang, Ning; Cheng, Sheue-yann; Zhang, Xiang; Tian, Qi; Pi, Jiangli; Tang, Jun; Huang, Qing; Wang, Feng; Chen, Jin; Xie, Zongyi; Xu, Zhongye; Chen, Weifu; Zheng, Huzhi; Yuan, Chao

doi:10.1016/j.nano.2016.08.029

Cited by 92 publications

(63 citation statements)

References 34 publications

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“…Cadmium‐containing quantum dots are known to be toxic, which is in large part attributed to the presence of free Cd 2+ ions released when non‐coated QDs are exposed to the acidic microenvironment after cellular uptake . Soenen and collaborators employed the degradation of cadmium quantum dots to correlate the loss of fluorescence intensity the number of cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics

et al. 2018

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Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab‐scale, batch‐to‐batch reproducible copper‐64‐ and gallium‐68‐radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water‐dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and 68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC‐3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO2 matrix represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes with high radiolabelling incorporation.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics

et al. 2018

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“…All mice in the saline, NIR, ILD, and iRGD‐ILD treatment groups died within 20 d. However, the survival rates of mice receiving iRGD‐ILD + NIR and ILD + NIR treatment were significantly prolonged. In details, 33.3% of ILD + NIR treated mice survived longer than 23 d, and 66.6% of iRGD‐ILD + NIR treated mice survived longer than 28 d. Admittedly, the limited penetration depth of light may hamper the application of phototherapy in intracranial tumor 18. However, light in the NIR range has several advantages over light in the visible range, and chief among them is its deeper tissue penetration due to less absorption by hemoglobin and water 19.…”

Section: Resultsmentioning

confidence: 99%

Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma

Xiao

Cai

et al. 2020

Adv Funct Materials

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Currently, treatment of intracranial diseases still remains a great challenge because the blood–brain barrier (BBB) blocks access of most drugs to the central nervous system. Herein, a theranostic small molecular probe, iRGD‐ICG‐Lys‐DTPA@Gd (iRGD‐ILD), capable of crossing BBB is developed. Owing to the small molecular size and αvβ3 integrin receptor–mediated transcytosis, this tailor‐made molecular probe integrating the fluorescence and magnetic resonance imaging functions effectively passes through BBB to target tumor cells even in the early stage of glioblastoma multiforme (GBM), thereby allowing a bimodal imaging–guided therapy of GBM. The reactive oxygen species and heat generated by the ICG moiety under the 808 nm laser irradiation exert photodynamic/photothermal therapeutic effects, which results in significantly inhibited tumor growth and prolonged median survival of C6‐Luc glioma‐bearing mice. Notably, the integration of FDA‐approved clinically available agents, e.g., ICG, DTPA and Gd, into a molecular probe may ensure desirable biocompatibility and biosafety for in vivo applications. Overall, the results highlight the potential of a water‐soluble small molecule as a novel theranostic probe for highly effective GBM treatment.

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“…Moreover, accumulated literature reports that the PEGylated NPs which are larger than our nanoprobe can pass the BBB. 38 QD-Apt was applied to label the EGFRvIII in vivo and in vitro in this study. The results suggested that QD-Apt could not only specially bind to the glioma cell lines expressing EGFRvIII but also connect to the EGFRvIII(+) glioma tissues with a high specificity in vitro and exhibit strong fluorescence intensity.…”

Section: Discussionmentioning

confidence: 99%

“…After centrifugation at 12,000 g for 15 min at 4°C, the supernatant (100 μL) was collected to determine the uptake of nanomaterials using a fluorescence plate reader. 38 Furthermore, the tumors and normal brain tissues were frozen and cut into 10-μm sections. After staining with GFAP antibody, fluorescence-conjugated secondary antibodies (green light), and DAPI (blue light), the sections were observed.…”

mentioning

confidence: 99%

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

Tang¹,

Huang²,

Zhang³

et al. 2017

IJN

Self Cite

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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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Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood–brain barrier and targeted fluorescence imaging of glioma and tumor vasculature

Cited by 92 publications

References 34 publications

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics

Molecular Probe Crossing Blood–Brain Barrier for Bimodal Imaging–Guided Photothermal/Photodynamic Therapies of Intracranial Glioblastoma

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

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