Cell surface clustering of heparan sulfate proteoglycans by amphipathic cell-penetrating peptides does not contribute to uptake

Verdurmen, Wouter P. R.; Wallbrecher, Rike; Schmidt, Samuel; Eilander, Jos; Bovée-Geurts, Petra H. M.; Fanghänel, Susanne; Bürck, Jochen; Wadhwani, Parvesh; Ulrich, Anne S.; Brock, Roland

doi:10.1016/j.jconrel.2013.05.001

Cited by 37 publications

(34 citation statements)

References 60 publications

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“…The protocol used in dynamics simulations is as follows: algorithm -Nos e-Poincar e-Andersen Hamiltonian equations of motion (NPA); temperatureconstant at 300°K; modeequilibration for 100 ps, forcefield -MMFF94X, cutoff at 8 A. Conformations were collected in trajectory files every 0.5 ps, providing 200 conformers for each run for each molecule. The molecular Chem Biol Drug Des 2014; 84: [24][25][26][27][28][29][30][31][32][33][34][35] dynamics simulations were also run in YASARA software (25) with similar results. Data analysis, such as distance measurement, was carried out also in MOE using the graphics interface.…”

Section: Molecular Modelingmentioning

confidence: 99%

A Bifurcated Proteoglycan Binding Small Molecule Carrier for siRNA Delivery

Gooding¹,

Adigbli²,

Chan³

et al. 2014

Chem Biol Drug Des

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A wider application of siRNA- and miRNA- based therapeutics is restricted by the currently available delivery systems. We have designed a new type of small molecule carrier (SMoC) system for siRNA modeled to interact with cell surface proteoglycans. This bifurcated SMoC has similar affinity for the model proteoglycan heparin to an equivalent polyarginine peptide and exhibits significant mRNA knockdown of protein levels comparable to lipofectamine and the previously reported linear SMoC.

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Section: Molecular Modelingmentioning

confidence: 99%

A Bifurcated Proteoglycan Binding Small Molecule Carrier for siRNA Delivery

Gooding¹,

Adigbli²,

Chan³

et al. 2014

Chem Biol Drug Des

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“…P-l-Arg as cationic cell penetrating peptide facilitated the rapid internalization of nanoplatforms through clathrin-mediated endocytosis into the cells. 32 P-l-Arg was able to directly interact with phosphates on the lipid part of membrane 16,32 and targeted the proteoglycan receptors, especially heparin sulfate on breast cancer cell lines which was overexpressed in cancer cells like MCF7. 19 To quantitatively estimate the cellular internalization of nanoplatform, the cells were incubated with GO-PEG-(P-l-Arg)/FITC and GO-PEG/ FITC before being analyzed by flow cytometry.…”

Section: Subcellular Localizationmentioning

confidence: 99%

“…Poly-l-arginine (P-l-Arg) and its derivatives have been considered as the major cell penetration peptides that mediates the import of different cargoes into the cells. 16,17 They have good interaction with phosphate groups presented on the cell membrane and target glycosaminoglycan receptors, especially heparin sulfate through multivalent interactions. 16,18 Glycosaminoglycan family receptors are overexpressed in cancerous cells, 19 which indicated a high affinity to targeted nanoplatforms for these receptors.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 They have good interaction with phosphate groups presented on the cell membrane and target glycosaminoglycan receptors, especially heparin sulfate through multivalent interactions. 16,18 Glycosaminoglycan family receptors are overexpressed in cancerous cells, 19 which indicated a high affinity to targeted nanoplatforms for these receptors. 17 Type and length of the targeting agents also indicate the impressive effect on the level of uptake.…”

Section: Introductionmentioning

confidence: 99%

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Cationic graphene oxide nanoplatform mediates miR-101 delivery to promote apoptosis by regulating autophagy and stress

Assali

Akhavan

Mottaghitalab

et al. 2018

IJN

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IntroductionMicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells.Materials and methodsIn this study, GO nanoplatforms were covalently decorated with polyethylene glycol (PEG) and poly-l-arginine (P-l-Arg) that reduced the surface of GO and increased the near infrared absorption ~7.5-fold higher than nonreduced GO.ResultsThe prepared nanoplatform [GO-PEG-(P-l-Arg)] showed higher miRNA payload and greater internalization and facilitated endosomal scape into the cytoplasm in comparison with GO-PEG. Furthermore, applying P-l-Arg, as a targeting agent, greatly improved the selective transfection of nanoplatform in cancer cells (MCF7, MDA-MB-231) in comparison with immortalized breast cells and fibroblast primary cells. Treating cancer cells with GO-PEG-(P-l-Arg)/miR-101 and incorporating near infrared laser irradiation induced 68% apoptosis and suppressed Stathmin1 protein.ConclusionThe obtained results indicated that GO-PEG-(P-l-Arg) would be a suitable targeted delivery system of miR-101 transfection that could downregulate autophagy and conduct thermal stress to activate apoptotic cascades when combined with photothermal therapy.

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“…A variety of membrane-destabilizing agents have been used to disrupt the endosomes and release the proteins from these vesicles [13][14][15]. But to date, these systems generally feature low delivery efficiency [16] or high toxicity [17,18].…”

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confidence: 99%

Intracellular Delivery of Proteins By Nanocarriers

Ray

Lee

Scaletti

et al. 2017

Nanomedicine (Lond.)

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Intracellular delivery of proteins is potentially a game-changing approach for therapeutics. However, for most applications, the protein needs to access the cytosol to be effective. A wide variety of strategies have been developed for protein delivery, however access of delivered protein to the cytosol without acute cytotoxicity remains a critical issue. In this review we discuss recent trends in protein delivery using nanocarriers, focusing on the ability of these strategies to deliver protein into the cytosol.

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Cell surface clustering of heparan sulfate proteoglycans by amphipathic cell-penetrating peptides does not contribute to uptake

Cited by 37 publications

References 60 publications

A Bifurcated Proteoglycan Binding Small Molecule Carrier for siRNA Delivery

A Bifurcated Proteoglycan Binding Small Molecule Carrier for siRNA Delivery

Cationic graphene oxide nanoplatform mediates miR-101 delivery to promote apoptosis by regulating autophagy and stress

Intracellular Delivery of Proteins By Nanocarriers

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