In vivo tumor imaging using a novel RNAi-based detection mechanism

Wan, Kayiu; Ebert, Bernd; Voigt, J.; Wang, Qing; Dai, Yiyang; Haag, Rainer; Kemmner, Wolfgang

doi:10.1016/j.nano.2012.02.004

Cited by 19 publications

(29 citation statements)

References 9 publications

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“…We developed dendritic polyglycerolamine (dPG-NH 2 ), a polyglycerol-based nanocarrier to deliver small interfering RNA (siRNA) and miRNA to tumors in vivo 30, 31, 32, 33. dPG-NH 2 is a cationic hyperbranched polymer, which improves siRNA stability, intracellular trafficking, silencing efficacy, and accumulation in the tumor environment due to the enhanced permeability and retention effect.…”

mentioning

confidence: 99%

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Ofek

Calderón

Mehrabadi

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG-NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood–brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2–miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2–miR-34a polyplex for brain-tumor treatment, with enhanced efficacy and no apparent signs of toxicity.

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confidence: 99%

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Ofek

Calderón

Mehrabadi

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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“…However, in a neoadjuvant setting there was a reduction in PpIX fluorescence in primary tumours, and a drastic reduction of fluorescent signal in metastases that resulted in not being able to discriminate between lymph nodes containing metastatic cells. In a follow-up study by Wan et al [139], conducted in xenografted nude mice, a novel siRNA-mediated knockdown of FECH was used to enhance the accumulation of PpIX, thereby increasing the endogenous fluorescence in tumour cells. While these results still need to be developed further, and tested in a clinical trial, they do hold promise for increasing the accuracy of early detection of primary and metastatic lesions and monitoring therapeutic response based on the size of the visualised tumour.…”

Section: Molecular Imagingmentioning

confidence: 99%

Prospects of ‘Omics Based Molecular Approaches in Colorectal Cancer Diagnosis and Treatment in the Developing World: A Case Study in Cape Town, South Africa

Adeola¹,

Goosen²,

Goldberg³

et al. 2014

Colorectal Cancer - Surgery, Diagnostics and Treatment

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“…In an interesting report, a new strategy for in vivo fluorescence imaging of siRNA delivery and therapy was developed using a tumor model [71]. Fluorescence imaging of the tumor tissue was made possible by RNAi-mediated downregulation of ferrochelatase, which led to accumulation of protoporphyrin IX, a fluorescent metabolite of heme synthesis (Fig.…”

Section: Imaging Rnai With Fluorescencementioning

confidence: 99%

“…ALA: 5-aminolevulinic acid; FECH: Ferrochelatase, the target for the siRNA used. Adapted with permission from [71]. …”

Section: Figurementioning

confidence: 99%

Multimodality Imaging of RNA Interference

Nayak¹,

Krasteva²,

Cai³

2013

CMC

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The discovery of small interfering RNAs (siRNAs) and their potential to knock down virtually any gene of interest has ushered in a new era of RNA interference (RNAi). Clinical use of RNAi faces severe limitations due to inefficiency delivery of siRNA or short hairpin RNA (shRNA). Many molecular imaging techniques have been adopted in RNAi-related research for evaluation of siRNA/shRNA delivery, biodistribution, pharmacokinetics, and the therapeutic effect. In this review article, we summarize the current status of in vivo imaging of RNAi. The molecular imaging techniques that have been employed include bioluminescence/fluorescence imaging, magnetic resonance imaging/spectroscopy, positron emission tomography, single-photon emission computed tomography, and various combinations of these techniques. Further development of non-invasive imaging strategies for RNAi, not only focusing on the delivery of siRNA/shRNA but also the therapeutic efficacy, is critical for future clinical translation. Rigorous validation will be needed to confirm that biodistribution of the carrier is correlated with that of siRNA/shRNA, since imaging only detects the label (e.g. radioisotopes) but not the gene or carrier themselves. It is also essential to develop multimodality imaging approaches for realizing the full potential of therapeutic RNAi, as no single imaging modality may be sufficient to simultaneously monitor both the gene delivery and silencing effect of RNAi.

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In vivo tumor imaging using a novel RNAi-based detection mechanism

Cited by 19 publications

References 9 publications

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex

Prospects of ‘Omics Based Molecular Approaches in Colorectal Cancer Diagnosis and Treatment in the Developing World: A Case Study in Cape Town, South Africa

Multimodality Imaging of RNA Interference

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