Antisense delivery using protamine-oligonucleotide particles

Junghans, Monika; Kreuter, Jörg; Zimmer, Andreas

doi:10.1093/nar/28.10.e45

Cited by 99 publications

(66 citation statements)

References 26 publications

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“…Moreover, we investigated constructs between gAd and protamine-oligonucleotide NPs, called proticles. Proticles are biodegradable NPs, which have been previously developed for the delivery of various active compounds like antisense oligonucleotides or small peptides (114)(115)(116)(117). They show a certain affinity to monocytes and macrophages which may be of additional interest for sequential AS plaque targeting.…”

Section: Adiponectin -An Anti-inflammatory Molecule Of Unconventionalmentioning

confidence: 99%

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Almer

Opriessnig

Ruth³

et al. 2014

European Journal of Nanomedicine

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Nanomedicine, a young and innovative field, offers interesting approaches for diagnosis and treatment in personalized medicine. Myocardial infarction and stroke belong to the most important challenges in this context because an improved early diagnosis of individuals well before fatal clinical endpoints occur is urgently needed. The underlying cause of myocardial infarction and stroke is atherosclerosis, a chronic immune-mediated inflammation of the vascular wall involving monocytes, macrophages, T-lymphocytes, and arterial wall cells. Hence, an immense number of pro-inflammatory mediators have been investigated in the context of nanomedicine and atherosclerosis but, interestingly, only few anti-inflammatory biomarkers. Nevertheless, the anti-inflammatory axis is always present as a negative feedback if a critical inflammatory perpetuation destabilizes atherosclerotic lesions. Hence, we could show that the immune-modulating, antiinflammatory molecules, adiponectin and interleukin-10, are useful for molecular imaging of AS plaques. Based on recent publications in animal models of atherosclerosis, we strongly assume that the inflammatory "brake" mechanisms may represent an interesting new tool to specifically target the scenario of culprit AS-lesions. In this review article we discuss the potential of adiponectin, interleukin-10 and other anti-inflammatory active molecules like targeted liposomes and high dense lipoproteins towards this.

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Section: Adiponectin -An Anti-inflammatory Molecule Of Unconventionalmentioning

confidence: 99%

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Almer

Opriessnig

Ruth³

et al. 2014

European Journal of Nanomedicine

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“…Proticles are biodegradable NPs which were developed and characterized by our group in the delivery of various active compounds such as antisense ONs or small peptides. [20][21][22][23] Proticles are formed by the spontaneous self-assembly of oppositely-charged biomolecules (protamine and ONs) in an aqueous solution. Once formed, proticles can also be coated with targeting sequences.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

Almer¹,

Summers²,

Scheicher³

et al. 2014

IJN

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Atherosclerosis (AS) is one of the leading causes of mortality in high-income countries. Early diagnosis of vulnerable atherosclerotic lesions is one of the biggest challenges currently facing cardiovascular medicine. The present study focuses on developing targeted nanoparticles (NPs) in order to improve the detection of vulnerable atherosclerotic-plaques. Various biomarkers involved in the pathogenesis of atherosclerotic-plaques have been identified and one of these promising candidates for diagnostic targeting is interleukin 10 (IL10). IL10 has been shown to be a key anti-inflammatory responding cytokine in the early stages of atherogenesis, and has already been used for therapeutic interventions in humans and mice. IL10, the targeting sequence, was coupled to two different types of NPs: protamine-oligonucleotide NPs (proticles) and sterically stabilized liposomes in order to address the question of whether the recognition and detection of atherosclerotic-lesions is primarily determined by the targeting sequence itself, or whether it depends on the NP carrier system to which the biomarker is coupled. Each IL10-targeted NP was assessed based on its sensitivity and selectivity toward characterizing atherosclerotic-plaque lesions using an apolipoprotein E-deficient mouse as the model of atherosclerosis. Aortas from apolipoprotein E-deficient mice fed a high fat diet, were stained with either fluorescence-labeled IL10 or IL10-coupled NPs. Ex vivo imaging was performed using confocal laser-scanning microscopy. We found that IL10-targeted proticles generated a stronger signal by accumulating at the surface of atherosclerotic-plaques, while IL10-targeted, sterically stabilized liposomes showed a staining pattern deeper in the plaque compared to the fluorescence-labeled IL10 alone. Our results point to a promising route for enhanced in vivo imaging using IL10-targeted NPs. NPs allow a higher payload of signal emitting molecules to be delivered to the atherosclerotic-plaques, thus improving signal detection. Importantly, this allows for the opportunity to visualize different areas within the plaque scenario, depending on the nature of the applied nanocarrier.

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“…Proticles are biodegradable nanoparticles, which have been previously developed and characterized by our group for the delivery of various active compounds, including antisense oligonucleotides or small peptides. [14][15][16][17] Proticles can be formulated by directed self-assembly of anionic and cationic biopolymers in combination with protamine, a cationic 32 amino acid peptide used in depot insulin. These nanoparticles can be coated with drug targeting sequences in a second production step.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques

Almer

Wernig²,

Saba-Lepek³

et al. 2011

IJN

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Background: Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd), which was used as a targeting sequence in this study. Methods: gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy. Results: gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of atherosclerotic plaques, while gAd-targeted proticles became internalized and showed more spotted plaque staining. Conclusion: Our results offer a promising perspective for enhanced in vivo imaging using gAd-targeted nanoparticles. By means of nanoparticles, a higher payload of signal emitting molecules could be transported to atherosclerotic plaques. Additionally, the opportunity is opened up to visualize different regions in the plaque scenario, depending on the nature of the nanoparticle used.

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Antisense delivery using protamine-oligonucleotide particles

Cited by 99 publications

References 26 publications

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques

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Antisense delivery using protamine-oligonucleotide particles

Cited by 99 publications

References 26 publications

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Anti-inflammatory mediators for molecular imaging of atherosclerosis

Interleukin 10-coated nanoparticle systems compared for molecular imaging of&nbsp;atherosclerotic lesions

Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques

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Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions