In Situ Functionalized Polymers for siRNA Delivery

Priegue, Juan M.; Crisan, Daniel N.; Martı́nez-Costas, José; Granja, Juan R.; Fernández-Trillo, Francisco; Montenegro, Javier

doi:10.1002/anie.201601441

Cited by 83 publications

(97 citation statements)

References 34 publications

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“…For this purpose we prepared egg yolk phosphatidylcholine (EYPC) large unilamellar vesicles (LUVs) loaded with the anionic fluorophore 8-hydroxy-1,3,6-pyrenetrisulfonate (HPTS) and the cationic quencher p-xylene-bispyridinium bromide (DPX) (Figure 2). 23,24 In this assay, the intravesicular concentrations of dye (HPTS) and quencher (DPX) are balanced to afford minimal emission of the resting state vesicles (see Supporting Informa- …”

Section: Syn Lettmentioning

confidence: 99%

Tuning the Properties of Penetrating Peptides by Oxime Conjugation

Pazo

Fernández-Caro

Priegue

et al. 2017

Synlett

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We here describe the application of oxime bond formation between a peptide scaffold and different aldehydes to modify the transporting capabilities of penetrating peptides. We show that bonds such as oximes offer a great synthetic advantage for the modification of the properties of model penetrating peptides. We believe that this approach will allow the development of improved intracellular delivery vehicles.

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Section: Syn Lettmentioning

confidence: 99%

Tuning the Properties of Penetrating Peptides by Oxime Conjugation

Pazo

Fernández-Caro

Priegue

et al. 2017

Synlett

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“…The results reported herein highlight the potential of the glycosylationo fp enetratingp eptides to modulatetheir activity. [17][18][19][20][21][22][23][24][25] Interesting penetrating properties were further discovered in different naturala nd artificial structures, such as polyprolines, [26] guanidinyl glycosides, [27,28] b-peptides, [29] peptiden ucleic acids (PNAs), [30] nonpeptidic guanidinylated dendritic structures, [31] self-assembled nanofibers, [32,33] synthetic polymers, [34][35][36][37] supramolecular structures, [38][39][40] and polydisulfides. [14] These studies also showed that oligolysines were less effective than that of the oligoarginines analogues, [15] and triggered the development of synthetic penetrating oligoarginines.…”

Section: Introductionmentioning

confidence: 99%

“…[14,16] Similaru ptake properties were found for the enantiomeric TAT [49][50][51][52][53][54][55][56][57] peptidea nd in penetrating peptoidsw ith guanidiniums ide chains anchored at the nitrogen of the amide group. [4,37,48,[50][51][52][53][54][55][56][57][58] However, despite all advances in the field, CPPs still have some limitations, mainly relatedt o their selectivity and toxicity. [17][18][19][20][21][22][23][24][25] Interesting penetrating properties were further discovered in different naturala nd artificial structures, such as polyprolines, [26] guanidinyl glycosides, [27,28] b-peptides, [29] peptiden ucleic acids (PNAs), [30] nonpeptidic guanidinylated dendritic structures, [31] self-assembled nanofibers, [32,33] synthetic polymers, [34][35][36][37] supramolecular structures, [38]…”

Section: Introductionmentioning

confidence: 99%

Glycosylated Cell‐Penetrating Peptides (GCPPs)

et al. 2019

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The cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell‐penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations, mainly related to their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. The uptake efficiency and intracellular distribution of these glycopeptides have been systematically characterized by means of flow cytometry and confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported herein highlight the potential of the glycosylation of penetrating peptides to modulate their activity.

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“…The development of the next generationo ft herapeutics, such as proteins, nucleic acids and antibodies, or their analogues, [1][2][3][4][5][6] has the potentialt or evolutionise chemical biology and medicine. However,t he transport of these large, hydrophilic and labile biomolecules constitutes ag reat challenge in comparison with traditional small-molecule therapies.…”

Section: Introductionmentioning

confidence: 99%

Where in the Cell Is our Cargo? Methods Currently Used To Study Intracellular Cytosolic Localisation

2018

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The internalisation and delivery of active substances into cells is a field of growing interest for chemical biology and therapeutics. As we move from small-molecule-based drugs towards bigger cargos, such as antibodies, enzymes, nucleases or nucleic acids, the development of efficient delivery systems becomes critical for their practical application. Different strategies and synthetic carriers have been developed; these include cationic lipids, gold nanoparticles, polymers, cell-penetrating peptides (CPPs), protein surface modification etc. However, all of these methodologies still present limitations relating to the precise targeting of the different intracellular compartments and, in particular, difficulties in access to the cellular cytosol. Additionally, the precise quantification of the cellular uptake of a compound is not enough to demonstrate delivery and/or functional activity. Therefore, methods to determine cellular distributions of cargos and carriers are of critical importance for identifying the barriers that are blocking the activity. Herein we survey the different techniques that can currently be used to track and to monitor the subcellular localisation of the synthetic compounds that we deliver inside cells.

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In Situ Functionalized Polymers for siRNA Delivery

Cited by 83 publications

References 34 publications

Tuning the Properties of Penetrating Peptides by Oxime Conjugation

Tuning the Properties of Penetrating Peptides by Oxime Conjugation

Glycosylated Cell‐Penetrating Peptides (GCPPs)

Where in the Cell Is our Cargo? Methods Currently Used To Study Intracellular Cytosolic Localisation

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