Supramolecular Assemblies for the Cytoplasmic Delivery of Antisense Oligodeoxynucleotide:  Polyion Complex (PIC) Micelles Based on Poly(ethylene glycol)-SS-Oligodeoxynucleotide Conjugate

Oishi, Motoi; Hayama, Tetsuya; Akiyama, Yoshitsugu; Takae, Seiji; Harada, Atsushi; Yamasaki, Yuichi; Nagatsugi, Fumi; Sasaki, Shigeki; Nagasaki, Yukio; Kataoka, Kazunori

doi:10.1021/bm050370l

Cited by 95 publications

(68 citation statements)

References 32 publications

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“…This was attributed to the fact that bPEI was able to mediate successful escape from the endosome. [176] Although the exact site of disulfide cleavage is still unclear, these approaches nevertheless show the usefulness of the attachment of endosomolytic agents via disulfide bonds.…”

Section: Disulfides For the Attachment Of Endosomolytic Agentsmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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Nucleic acids are not only expected to assume a pivotal position as "drugs" in the treatment of genetic and acquired diseases, but could also act as molecular cues to control the microenvironment during tissue regeneration. Despite this promise, the efficient delivery of nucleic acids to their side of action is still the major hurdle. One among many prerequisites for a successful carrier system for nucleic acids is high stability in the extracellular environment, accompanied by an efficient release of the cargo in the intracellular compartment. A promising strategy to create such an interactive delivery system is to exploit the redox gradient between the extra- and intracellular compartments. In this review, emphasis is placed on the biological rationale for the synthesis of redox sensitive, disulfide-based carrier systems, as well as the extra- and intracellular processing of macromolecules containing disulfide bonds. Moreover, the basic synthetic approaches for introducing disulfide bonds into carrier molecules, together with examples that demonstrate the benefit of disulfides at the individual stages of nucleic acid delivery, will be presented.

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Section: Disulfides For the Attachment Of Endosomolytic Agentsmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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“…Results indicated that the fabricated smart micelles demonstrated significant antisense effect via disulfide bond cleavage in the cellular interior. This was because the delivery system crosslinked using disulfide linkages "sensed" high glutathione concentrations in the cellular cytoplasmic compartment [239].…”

Section: 32mentioning

confidence: 99%

Smart polymeric gels: Redefining the limits of biomedical devices

Chaterji

Kwon

Park

2007

Progress in Polymer Science

550

364

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This review describes recent progresses in the development and applications of smart polymeric gels, especially in the context of biomedical devices. The review has been organized into three separate sections: defining the basis of smart properties in polymeric gels; describing representative stimuli to which these gels respond; and illustrating a sample application area, namely, microfluidics. One of the major limitations in the use of hydrogels in stimuli-responsive applications is the diffusion rate limited transduction of signals. This can be obviated by engineering interconnected pores in the polymer structure to form capillary networks in the matrix and by downscaling the size of hydrogels to significantly decrease diffusion paths. Reducing the lag time in the induction of smart responses can be highly useful in biomedical devices, such as sensors and actuators. This review also describes molecular imprinting techniques to fabricate hydrogels for specific molecular recognition of target analytes. Additionally, it describes the significant advances in bottom-up nanofabrication strategies, involving supramolecular chemistry. Learning to assemble supramolecular structures from nature has led to the rapid prototyping of functional supramolecular devices. In essence, the barriers in the current performance potential of biomedical devices can be lowered or removed by the rapid convergence of interdisciplinary technologies.

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“…Displacement of nucleic acids by intracellular polyanions is likely to result in their unpacking for cationic lipids or polymers (449). The reducing environment or acidic conditions inside endosome/lysosomes within the cells have been exploited to provide extracellular stability to the nucleic acids, while the carrier molecules should be eliminated from the cell after internalization (450)(451)(452). For example, degradable PEI has been synthesized using low molecular weight PEI (1.8kDa), which has much lower cytotoxicity and nucleic acid condensing capability compared to large molecular weight PEI (25kDa) (452).…”

Section: Cellular Uptake and Subcellular Traffickingmentioning

confidence: 99%

“…The ODN/PEI polyelectrolyte complex forms an inner core while PEG chains surround it as a shell. Different linkage (glutathione-sensitive SS linkage, pH-sensitive linkage and thiomaleimide linkage) in the conjugates also substantially affected biological effects of the micelles (451,503). The use of PEGylated ODNs in combination with lipids could significantly improve the stability of complexes against serum (504).…”

Section: 32mentioning

confidence: 99%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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Supramolecular Assemblies for the Cytoplasmic Delivery of Antisense Oligodeoxynucleotide: Polyion Complex (PIC) Micelles Based on Poly(ethylene glycol)-SS-Oligodeoxynucleotide Conjugate

Cited by 95 publications

References 32 publications

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

Smart polymeric gels: Redefining the limits of biomedical devices

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

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