Fatty acid modified octa-arginine for delivery of siRNA

Li, Yuhuan; Li, Yujing; Wang, Xinmei; Lee, Robert J.; Teng, Lirong

doi:10.1016/j.ijpharm.2015.09.006

Cited by 33 publications

(26 citation statements)

References 42 publications

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“…44 siRNA displaced by heparin can bind to EB, where fluorescence emission is captured when excited. 7 As shown in Figure 3B, no siRNA released from LR or PSLR was observed when the N/P ratio reached 5, whereas a fractional release occurred from EPSLR at this ratio. The results indicated that the interactions between L or PSL and siRNA were stronger than EPSLR, thereby resisting dissociation, and this might be due to the high negative charge on the anti-EphA10 antibody diminishing siRNA-liposome interaction to some degree.…”

Section: Gel Retardation Assaymentioning

confidence: 73%

“…The stability of LR, PSLR, and EPSLR was evaluated using polyanion heparin 7 and FBS. LR, PSLR, and EPSLR were prepared at N/P ratios of 1, 2, 3, 5, 7, 9, and 14 as in the "Preparation of EPSLR nanocomplexes" section and then incubated with heparin solution (Tianjin Biochem Pharmaceutical Co. Ltd., Tianji, People's Republic of China) at a heparin/siRNA ratio of 5 (IU/μg) for 20 minutes at room temperature.…”

Section: Stability Assay Of the Sirna-liposome Complexesmentioning

confidence: 99%

“…Maximum therapeutic efficacy of siRNA can be obtained if the siRNAs are delivered to the site of action. 6,7 However, a variety of physiological, cellular, and immunological barriers hinder siRNA molecules from reaching their target site. 8 Physiological barriers are composed of endothelial barrier, degradation by nucleases, reticuloendothelial system uptake, etc.…”

Section: Introductionmentioning

confidence: 99%

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Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Zang¹,

Ding²,

Zhao³

et al. 2016

IJN

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Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol–Schiff base–polyethylene glycol (Chol–SIB–PEG)-modified cationic liposome–siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol–SIB–PEG was successfully synthesized and confirmed with FTIR and 1 H-NMR. An Eph–PEG–SIB–Chol-modified liposome–siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application.

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Section: Gel Retardation Assaymentioning

confidence: 73%

Section: Stability Assay Of the Sirna-liposome Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Zang¹,

Ding²,

Zhao³

et al. 2016

IJN

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“…[ 1 ] The same principle has been widely applied to enhance the internalization of cell‐penetrating peptides (CPPs), for example, by the incorporation of hydrophobic residues such as phenylalanine or tyrosine. [ 2,3 ] Ever since the first report of gene therapy by Merril et al in 1971, one of the pressing challenges we still face is the invention of an efficient non‐viral delivery vector that can transport genetic materials inside living cells. [ 4 ] The design of such synthetic vectors is often inspired by nature and it is frequently based on cationic macromolecules with well‐defined molecular weight, dispersity, and functionality.…”

Section: Polymer Samples Experimental [Mol%] Mnexperimental [G Mol–1]mentioning

confidence: 99%

Incorporation of Indole Significantly Improves the Transfection Efficiency of Guanidinium‐Containing Poly(Methacrylamide)s

Cokca

Zartner

Tabujew

et al. 2020

Macromol. Rapid Commun.

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A highly efficient transfection agent is reported that is based on terpolymer consisting of N‐(2‐hydroxypropyl)methacrylamide (HPMA), N‐(3‐guanidinopropyl) methacrylamide (GPMA), and N‐(2‐indolethyl)methacrylamide monomers (IEMA) by analogy to the amphipathic cell‐penetrating peptides containing tryptophan and arginine residues. The incorporation of the indole‐bearing monomer leads to successful plasmid DNA condensation even at a nitrogen‐to‐phosphate (N/P) ratio of 1. The hydrodynamic diameter of polyplexes is determined to be below 200 nm for all N/P ratios. The transfection studies demonstrate a 200‐fold increase of the transgene expression in comparison to P(HPMA‐co‐GPMA) with the same guanidinium content. This study reveals the strong potential of the indole group as a side‐chain pendant group that can increase the cellular uptake of polymers and the transfection efficiency of the respective polyplexes.

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“…It was demonstrated that simple modification of octaarginine (R8) with a long chain fatty acid promotes siRNA condensation, and the resulting highly condensed nanoparticle shows improved stability against particle disassembly and enzymatic degradation [26]. Furthermore, the complex using modified R8 also exhibits 40–50 times higher cell uptake than the unmodified R8 [27]. …”

Section: Cell Penetrating Peptides: Sirna Intracellular Uptakementioning

confidence: 99%

Functional peptides for siRNA delivery

Tai

Gao

2017

Advanced Drug Delivery Reviews

158

120

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siRNA is considered as a potent therapeutic agent because of its high specificity and efficiency in suppressing genes that are overexpressed during disease development. For nearly two decades, a significant amount of efforts has been dedicated to bringing the siRNA technology into clinical uses. However, only limited success has been achieved to date, largely due to the lack of a cell type-specific, safe, and efficient delivery technology to carry siRNA into the target cells' cytosol where RNA interference takes place. Among the emerging candidate nanocarriers for siRNA delivery, peptides have gained popularity because of their structural and functional diversity. A variety of peptides have been discovered for their ability to translocate siRNA into living cells via different mechanisms such as direct penetration through the cellular membrane, endocytosis-mediated cell entry followed by endosomolysis, and receptor-mediated uptake. This review is focused on the multiple roles played by peptides in siRNA delivery, such as membrane penetration, endosome disruption, targeting, as well as the combination of these functionalities.

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Fatty acid modified octa-arginine for delivery of siRNA

Cited by 33 publications

References 42 publications

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA

Incorporation of Indole Significantly Improves the Transfection Efficiency of Guanidinium‐Containing Poly(Methacrylamide)s

Functional peptides for siRNA delivery

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