A convergent uptake route for peptide- and polymer-based nucleotide delivery systems

Lindberg, Staffan; Regberg, Jakob; Eriksson, Jonas; Helmfors, Henrik; Muñoz-Alarcón, Andrés; Srimanee, Artita; Figueroa, Ricardo; Hallberg, Einar; Ezzat, Kariem; Langel, Ülo

doi:10.1016/j.jconrel.2015.03.009

Cited by 36 publications

(20 citation statements)

References 30 publications

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“…A recent study showed that the cellular uptake of CPP/oligonucleotide nanocomplexes involves scavenger receptors (226). Another interesting report demonstrated that the NPC1 lipid transport system, previously shown to be involved in LNP processing (158), is also involved in the processing of certain types of polymeric nanoparticles (227).…”

Section: Approaches To Deliverymentioning

confidence: 99%

The delivery of therapeutic oligonucleotides

2016

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The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.

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Section: Approaches To Deliverymentioning

confidence: 99%

The delivery of therapeutic oligonucleotides

2016

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“…This class of innate immune receptors is known to bind negatively charged particulate ligands [110]. Other scavenger-related receptors, such as lipoprotein receptor-related protein (LRP), have been previously shown to be involved in the uptake of Tat peptide [111], and recently several studies have demonstrated the involvement of different classes of scavenger or scavenger-related receptors such as SCARAs, scavenger receptor cysteine-rich type I (M160) and SR-BI in the uptake of CPPs with different cargos including NicFects, CADY and even with cationic polymers such as PEI [112][113][114][115].…”

Section: Uptake Pathways Of Cpp and Nucleic Acid Conjugates And Nanopmentioning

confidence: 99%

Peptides for nucleic acid delivery

Lehto

Ezzat

Wood

et al. 2016

Advanced Drug Delivery Reviews

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196

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Nucleic acids and their synthetic oligonucleotide (ON) analogs are a group of gene therapeutic compounds which hold enormous clinical potential. Despite their undoubted potential, clinical translation of these molecules, however, has been largely held back by their limited bioavailability in the target tissues/cells. To overcome this, many different drug delivery systems have been devised. Among others, short delivery peptides, called cell-penetrating peptides (CPPs), have been demonstrated to allow for efficient delivery of nucleic acids and their ON analogs, in both cell culture and animal models. In this review, we provide brief overview of the latest advances in nucleic acid delivery with CPPs, covering the two main vectorization strategies, covalent conjugation and nanoparticle formation-based approach. In conclusion, CPP-based drug delivery systems have the capacity to overcome the hurdle of delivery and thus have the potential to facilitate the clinical translation of nucleic acid-based therapeutics.

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“…Also, other types of CPPs form negatively charged complexes with NA payloads under physiologic conditions, and their uptake is mediated by SRs, as recently shown by several groups (10)(11)(12)(13). Moreover, SRspecific inhibitory ligands, like poly-I and dextran sulfate, block transfection of cells with the commercial transfectants polyethyleneimine and poly-L-ornithine by abolishing the cellular uptake of their complexes with NA (13). These results suggest that SR-dependent internalization is a rather general mechanism for the cellular uptake of CPP-NA nanoparticles and for polycationic agents used for transfection of cells.…”

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confidence: 83%

“…Recently, it has been shown that the SR-specific inhibitory ligands poly-I and dextran sulfate reduce the association of fluorescently labeled PF14 with HeLa and other cells and subsequent internalization (13), suggesting that SRs may also recognize free CPPs. In concordance with this, we found that PF14 also promoted the translocation of SR-A3s and SR-A5s from the endomembranes of the cytoplasm to the plasma membrane of HeLa cells (Fig.…”

Section: Cpps Induce Translocation Of Sr-a3s and Sr-a5s To The Cell Smentioning

confidence: 99%

“…SR-As belong to the group of type II transmembrane glycoproteins that assist in the endocytosis of a very diverse array of anionic ligands (8,9). Also, other types of CPPs form negatively charged complexes with NA payloads under physiologic conditions, and their uptake is mediated by SRs, as recently shown by several groups (10)(11)(12)(13). Moreover, SRspecific inhibitory ligands, like poly-I and dextran sulfate, block transfection of cells with the commercial transfectants polyethyleneimine and poly-L-ornithine by abolishing the cellular uptake of their complexes with NA (13).…”

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confidence: 99%

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Cell‐penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids

et al. 2016

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Scavenger receptors (SRs) are a large family of multifunctional receptors that are involved in a range of physiologic and pathologic processes. The ability of class A scavenger receptors (SR-As) to bind anionic ligands facilitates the internalization of negatively charged cell-penetrating peptide (CPP)-nucleic acid nanocomplexes and thus makes them attractive targets for delivery of various nucleic acids. Recently, we demonstrated that SR-A3 and SR-A5 are recruited from intracellular membranes to the plasma membrane after incubation with PepFect 14-splice-switching oligonucleotide complexes. Here, we examined the mechanisms responsible for translocation of SR-As to the cell surface. We demonstrate that, in addition to nanocomplexes, some amphipathic CPPs are able to induce externalization of SR-A3 and SR-A5, and this process requires the presence of calcium ions. Furthermore, translocation of SR-A3 and SR-A5 requires activity of phosphatidylinositol-3-kinase, intact actin cytoskeleton, and the presence of serum proteins in culture medium.-Juks, C., Lorents, A., Arukuusk, P., Langel, Ü., Pooga, M. Cell-penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids.

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A convergent uptake route for peptide- and polymer-based nucleotide delivery systems

Cited by 36 publications

References 30 publications

The delivery of therapeutic oligonucleotides

The delivery of therapeutic oligonucleotides

Peptides for nucleic acid delivery

Cell‐penetrating peptides recruit type A scavenger receptors to the plasma membrane for cellular delivery of nucleic acids

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