Biophysical properties of chitosan/siRNA polyplexes: Profiling the polymer/siRNA interactions and bioactivity

Holzerny, Pascale; Ajdini, Baskim; Heusermann, Wolf; Bruno, Katharina; Schuleit, Michael; Meinel, Lorenz; Keller, Michael

doi:10.1016/j.jconrel.2011.08.023

Cited by 80 publications

(83 citation statements)

References 34 publications

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“…17,18,21,24 These kinetics and intracellular behaviors are in good agreement with the results using similar carriers. [23][24][25] In our previous study, Py-AA-TO was shown to selectively visualize the siRNA encapsulated in a polymer-based carrier. 11 We thus examined whether the fluorescence signal of Py-AA-TO could be a good indicator to assess not only cellular uptake but also the disassembly of the polyplex.…”

Section: Resultssupporting

confidence: 87%

“…From these results, the polyplexes containing siGL2 affnity-labeled with Py-AA-TO were taken up via endocytosis and most of the polyplexes were sequestrated in lysosome, as was typically observed in various kinds of siRNAcontaining polyplexes. [22][23][24] We found affinity-labeling with Py-AA-TO was applicable to time-lapse analysis of cellular uptake and subcellular trafficking of the polyplexes (Fig. 4).…”

Section: Resultsmentioning

confidence: 97%

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Fluorescence Imaging of siRNA Delivery by Peptide Nucleic Acid-based Probe

Sato

Iwai

et al. 2015

ANAL. SCI.

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We report on the use of a peptide nucleic acid (PNA)-based fluorescent probe for the analysis of siRNA delivery to living cells. The probe, Py-AA-TO, possesses thiazole orange (TO) and pyrene moieties in the C-and N-termini of PNA, and can function as a light-up probe capable of selective binding to 3′-overhanging nucleotides of target siRNAs. The affinitylabeling of the siRNAs with Py-AA-TO facilitates fluorescence imaging of cellular uptake of polymer-based carriers encapsulating the siRNAs (polyplexes) through endocytosis and subsequent sequestration into lysosome. In addition, flow cytometric measurements reveal that the monitoring of Py-AA-TO fluorescence inside the cells is successfully applicable to the analysis of the polyplex disassembly. These promising functions of Py-AA-TO are presented and discussed as a basis for the design of molecular probes for fluorescent imaging and quantitative analysis of the siRNA delivery process.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 97%

Fluorescence Imaging of siRNA Delivery by Peptide Nucleic Acid-based Probe

Sato

Iwai

et al. 2015

ANAL. SCI.

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“…Chitosan is a polycationic, nontoxic, mucoadhesive polymer, which has been proven safe for use in vivo [33]. It has been widely used to mediate intracellular uptake of nucleic acids [34]. Moreover, the polycation polyplexes were found to enhance their internalization by cells mediating the interaction of nonspecific charges with membrane proteoglycans, and the highly monodispersed nanoparticles were reported to be passively accumulated and retained at the tissue sites [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Development of Chitosan/Heparin Nanoparticle-Encapsulated Cytolethal Distending Toxin for Gastric Cancer Therapy

et al. 2014

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“…However, polymer based nanoparticles have shown to be suitable for the delivery of siRNA and have become an exciting field of siRNA delivery research (Zhang et al, 2007). Because of the adhesive properties of chitosan, which facilitate its nonparenteral pulmonary, nasal and oral administration a variety of chitosan nanocarriers have been utilized for the delivery of macromolecules (Csaba et al, 2009;Krauland and Alonso, 2007) and siRNA (Holzerny et al, 2012;Jørgensen et al, 2012). Chitosan modifications have been introduced to increase the efficiency of siRNA intracellular delivery and to reduce toxicity.…”

Section: Discussionmentioning

confidence: 99%

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

Matokanović

Barišić

Filipović-Grčić

et al. 2013

European Journal of Pharmaceutical Sciences

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a b s t r a c tInducers of heat shock protein 70 (Hsp70) commonly promote cancer cell viability whereas inhibitors of Hsp90 reduce it. The anticancer agent celastrol, interferes with signal transduction pathways involving these heat shock proteins. The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol-induced tumor cell death. Hsp70 siRNA loaded chitosan-TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field-flow fractionation combined with dynamic light scattering. Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan-TPP-Hsp70 siRNA particles. The results showed that silencing of Hsp70 by chitosan-TPP-Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative effects of celastrol in leukemia and glioblastoma cells. In glioblastoma spheroids, higher concentrations of celastrol and Hsp70 siRNA in chitosan-TPP nanocarriers were necessary to induce cell death.

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Biophysical properties of chitosan/siRNA polyplexes: Profiling the polymer/siRNA interactions and bioactivity

Cited by 80 publications

References 34 publications

Fluorescence Imaging of siRNA Delivery by Peptide Nucleic Acid-based Probe

Fluorescence Imaging of siRNA Delivery by Peptide Nucleic Acid-based Probe

Development of Chitosan/Heparin Nanoparticle-Encapsulated Cytolethal Distending Toxin for Gastric Cancer Therapy

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

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