Liposome based systems for systemic siRNA delivery: Stability in blood sets the requirements for optimal carrier design

Buyens, Kevin; Smedt, Stefaan C. De; Braeckmans, Kevin; Demeester, Joseph; Peeters, Liesbeth; Grunsven, Leo A. van; Jeu, Xavier de Mollerat du; Sawant, Rupa R.; Torchilin, Vladimir P.; Farkasova, Katarina; Ogris, Manfred; Sanders, Niek N.

doi:10.1016/j.jconrel.2011.10.009

Cited by 176 publications

(124 citation statements)

References 73 publications

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“…[10][11][12][13][14][15] Among the various systems studied, the lipid-based delivery system has received more attention as a promising carrier for siRNA delivery owing to its simplicity of production, relatively low immunogenicity, and absence of oncogenicity. [16][17][18][19] The liposome-polycation-DNA complex (LPD) system, prepared by condensing the siRNA and DNA with protamine into a compact complex followed by coating with cationic liposomes, is an effective lipidic nanovector for systemic siRNA delivery, and was developed in 1996 by Lee and Huang. 2 To overcome the kinetic and physical barriers to systemic siRNA delivery, it is necessary to develop PEGylated immunoliposomes conjugated with targeting ligands.…”

Section: Introductionmentioning

confidence: 99%

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Deng¹,

Zhang²,

Ma³

et al. 2013

IJN

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Section: Introductionmentioning

confidence: 99%

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Deng¹,

Zhang²,

Ma³

et al. 2013

IJN

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“…6,9 To evaluate the inflammatory cytokine response mediated by lipoplexes or LNPs, cellular uptake efficiency by Figure 4A). The extents of TNF-α release triggered by lipoplexes or LNPs were higher than those obtained with cationic liposomes that did not carry siRNA ( Figure 4B).…”

Section: Immune Stimulationmentioning

confidence: 99%

“…53 This indicates that the inflammatory response is related to cell internalization of siRNA-loaded carriers because these TLRs are known to localize on the endosomal membrane. 6,9,53 On the other hand, Kedmi et al reported cytokine release, including both TNF-α and IL-1β by positively charged lipid nanoparticles via stimulation of TLR4 in addition to immune stimulation by nucleic acids, and TLR4 is known to localize on the cell surface. 54 In this study, because the released amount of TNF-α was higher as the N/P ratio was lower, TLRs 3, 7, and 8 in the cells that recognize the nucleic acid were likely to be involved.…”

mentioning

confidence: 99%

Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

Kubota¹,

Onishi²,

Sawaki³

et al. 2017

IJN

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Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state; however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-α, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-α and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly; therefore, nanoformulations should be optimized before extending studies into the in vivo environment.

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“…Although there are other polymers that can be used for these purposes, including dextran, PEG has been commonly used to coat a number of types of nanocarriers, including liposomes, [51][52][53] polymeric nanoparticles, 54 metallic organic particles, [55][56][57] micelles, [58][59][60][61][62][63] and carbon nanotubes. [64][65][66][67][68] The preferential use of PEG for the synthesis of DDS over other polymers is mainly due to the fact that it can be further functionalized with both organic and inorganic moieties.…”

Section: Immunocompatibility Of Polymeric Particles Peg Chain Densitymentioning

confidence: 99%

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

Khorasani¹,

Weaver²,

Salvador-Morales³

2014

IJN

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On the cusp of widespread permeation of nanomedicine, academia, industry, and government have invested substantial financial resources in developing new ways to better treat diseases. Materials have unique physical and chemical properties at the nanoscale compared with their bulk or small-molecule analogs. These unique properties have been greatly advantageous in providing innovative solutions for medical treatments at the bench level. However, nanomedicine research has not yet fully permeated the clinical setting because of several limitations. Among these limitations are the lack of universal standards for characterizing nanomaterials and the limited knowledge that we possess regarding the interactions between nanomaterials and biological entities such as proteins. In this review, we report on recent developments in the characterization of nanomaterials as well as the newest information about the interactions between nanomaterials and proteins in the human body. We propose a standard set of techniques for universal characterization of nanomaterials. We also address relevant regulatory issues involved in the translational process for the development of drug molecules and drug delivery systems. Adherence and refinement of a universal standard in nanomaterial characterization as well as the acquisition of a deeper understanding of nanomaterials and proteins will likely accelerate the use of nanomedicine in common practice to a great extent.

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Liposome based systems for systemic siRNA delivery: Stability in blood sets the requirements for optimal carrier design

Cited by 176 publications

References 73 publications

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

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Liposome based systems for systemic siRNA delivery: Stability in blood sets the requirements for optimal carrier design

Cited by 176 publications

References 73 publications

Comparison of anti-EGFR-Fab&rsquo; conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Comparison of anti-EGFR-Fab&rsquo; conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

Contact Info

Product

Resources

About

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells

Comparison of anti-EGFR-Fab’ conjugated immunoliposomes modified with two different conjugation linkers for siRNA delivery in SMMC-7721 cells