Transporting silence: Design of carriers for siRNA to angiogenic endothelium

Schiffelers, Raymond M.; Mixson, A. James; Ansari, Aslam M.; Fens, Marcel H.A.M.; Tang, Quingquan; Zhou, Qin; Xu, Jun; Molema, Grietje; Lu, Patrick Y.; Scaria, Puthupparampil V.; Storm, Gert; Woodle, Martin C.

doi:10.1016/j.jconrel.2005.05.018

Cited by 84 publications

(87 citation statements)

References 33 publications

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“…Although advances are being made (1)(2)(3), currently, only a few approaches potentially feasible in patients have been described (4)(5)(6)(7)(8). Our laboratory has developed an anti-transferrin receptor (TfR) single-chain antibody fragment-directed nanoimmunoliposome (scL), which self-assembles into f100-nm size particles.…”

Section: Introductionmentioning

confidence: 99%

Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System

et al. 2007

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Section: Introductionmentioning

confidence: 99%

Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System

et al. 2007

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“…Effective in vivo delivery of siRNA to the appropriate target cell is an essential component of these siRNA-based applications. Accordingly, a variety of nonviral (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and viral (15)(16)(17) systems are being developed for delivery of siRNA to liver, tumors, and other tissues in vivo.…”

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confidence: 99%

Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes

Rozema

Lewis

Wakefield

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Achieving efficient in vivo delivery of siRNA to the appropriate target cell would be a major advance in the use of RNAi in gene function studies and as a therapeutic modality. Hepatocytes, the key parenchymal cells of the liver, are a particularly attractive target cell type for siRNA delivery given their central role in several infectious and metabolic disorders. We have developed a vehicle for the delivery of siRNA to hepatocytes both in vitro and in vivo, which we have named siRNA Dynamic PolyConjugates. Key features of the Dynamic PolyConjugate technology include a membrane-active polymer, the ability to reversibly mask the activity of this polymer until it reaches the acidic environment of endosomes, and the ability to target this modified polymer and its siRNA cargo specifically to hepatocytes in vivo after simple, low-pressure i.v. injection. Using this delivery technology, we demonstrate effective knockdown of two endogenous genes in mouse liver: apolipoprotein B (apoB) and peroxisome proliferator-activated receptor alpha (ppara). Knockdown of apoB resulted in clear phenotypic changes that included a significant reduction in serum cholesterol and increased fat accumulation in the liver, consistent with the known functions of apoB. Knockdown of ppara also resulted in a phenotype consistent with its known function, although with less penetrance than observed in apoB knockdown mice. Analyses of serum liver enzyme and cytokine levels in treated mice indicated that the siRNA Dynamic PolyConjugate was nontoxic and well tolerated.pH labile bonds ͉ nonviral siRNA delivery ͉ siRNA-polymer conjugates ͉ endosomolytic polymers

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“…Furthermore, QDs have been shown to be useful in guided surgery, 27 and recently the combination of an optical and MR detectable probe has been proposed to be useful in this field. 28 The RGD peptide has been proven useful in drug and gene targeting in vivo 29,30 and in the field of molecular imaging. Conjugates of RGD have been used for the identification of angiogenesis with PET, 25 whereas paramagnetic perfluorcarbon nanoparticles carrying RGD mimetics 31 and paramagnetic bimodal liposomes 6 conjugated to cyclic RGD peptides 7 have shown their potential for the in vivo detection of the Rv 3 integrins with MRI.…”

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Quantum Dots with a Paramagnetic Coating as a Bimodal Molecular Imaging Probe

et al. 2005

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MRI detectable and targeted quantum dots were developed. To that aim, quantum dots were coated with paramagnetic and pegylated lipids, which resulted in a relaxivity, r 1 , of nearly 2000 mM -1 s -1 per quantum dot. The quantum dots were functionalized by covalently linking rv 3-specific RGD peptides, and the specificity was assessed and confirmed on cultured endothelial cells. The bimodal character, the high relaxivity, and the specificity of this nanoparticulate probe make it an excellent contrast agent for molecular imaging purposes.

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Transporting silence: Design of carriers for siRNA to angiogenic endothelium

Cited by 84 publications

References 33 publications

Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System

Materializing the Potential of Small Interfering RNA via a Tumor-Targeting Nanodelivery System

Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes

Quantum Dots with a Paramagnetic Coating as a Bimodal Molecular Imaging Probe

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