Peptide-mediated Delivery: an Overview of Pathways for Efficient Internalization

Pae, Janely; Pooga, Margus

doi:10.4155/tde.14.72

Cited by 19 publications

(17 citation statements)

References 159 publications

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“…Although electroporation, microinjection, lipid-based transfection, and viral vectors have already been widely used, they still have drawbacks such as inefficient, cytotoxic, complex, penurious bioavailability and unreliable for in vivo studies [1, 2]. Thus, many alternative approaches [3–5] especially peptide-based transduction for foreign bioactive molecule delivery have been discovered and exploited.…”

Section: Introductionmentioning

confidence: 99%

Efficient therapeutic delivery by a novel cell-permeant peptide derived from KDM4A protein for antitumor and antifibrosis

Wang

Yang

et al. 2016

Oncotarget

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Cell-penetrating peptide (CPP) based delivery have provided immense potential for the therapeutic applications, however, most of nonhuman originated CPPs carry the risk of possible cytotoxicity and immunogenicity, thus may restricting to be used. Here, we describe a novel human-derived CPP, denoted hPP10, and hPP10 has cell-penetrating properties evaluated by CellPPD web server, as well as In-Vitro and In-Vivo analysis. In vitro studies showed that hPP10-FITC was able to penetrate into various cells including primary cultured cells, likely through an endocytosis pathway. And functionalized macromolecules, such as green fluorescent protein (GFP), tumor-specific apoptosis inducer Apoptin as well as biological active enzyme GCLC (Glutamate-cysteine ligase, catalytic subunit) can be delivered by hPP10 in vitro and in vivo. Collectively, our results suggest that hPP10 provide a novel and versatile tool to deliver exogenous proteins or drugs for clinical applications as well as reprogrammed cell-based therapy.

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Section: Introductionmentioning

confidence: 99%

Efficient therapeutic delivery by a novel cell-permeant peptide derived from KDM4A protein for antitumor and antifibrosis

Wang

Yang

et al. 2016

Oncotarget

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“…For successful polynucleotide delivery, a vehicle should fulfill three requirements: (1) delivery to the desired tissue, (2) release of cargo into the cytoplasm, and (3) low toxicity. Cell-penetrating peptides have been proved to satisfy all of these requirements, delivering siRNA and peptides to cells,56, 69 with an increasing number of peptides used for this purpose 34, 47, 70, 71, 72, 73. Some CPPs have been used in vivo to deliver siRNA, targeting tumors, the brain-blood barrier, and other tissues,74, 75 but none was topically applied, either to the skin or to the ocular surface 34 .…”

Section: Discussionmentioning

confidence: 99%

Effective In Vivo Topical Delivery of siRNA and Gene Silencing in Intact Corneal Epithelium Using a Modified Cell-Penetrating Peptide

Schiroli¹,

Gómara

Maurizi³

et al. 2019

Molecular Therapy - Nucleic Acids

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Autosomal dominantly inherited genetic disorders such as corneal dystrophies are amenable to allele-specific gene silencing with small interfering RNA (siRNA). siRNA delivered to the cornea by injection, although effective, is not suitable for a frequent long-term treatment regimen, whereas topical delivery of siRNA to the cornea is hampered by the eye surface’s protective mechanisms. Herein we describe an attractive and innovative alternative for topical application using cell-penetrating peptide derivatives capable of complexing siRNA non-covalently and delivering them into the cornea. Through a rational design approach, we modified derivatives of a cell-penetrating peptide, peptide for ocular delivery (POD), already proved to diffuse into the corneal layers. These POD derivatives were able to form siRNA-peptide complexes (polyplexes) of size and ζ-potential similar to those reported able to undergo cellular internalization. Successful cytoplasmic release and gene silencing in vitro was obtained when an endosomal disruptor, chloroquine, was added. A palmitoylated-POD, displaying the best delivery properties, was covalently functionalized with trifluoromethylquinoline, an analog of chloroquine. This modified POD, named trifluoromethylquinoline-palmitoyl-POD (QN-Palm-POD), when complexed with siRNA and topically applied to the eye in vivo , resulted in up to 30% knockdown of luciferase reporter gene expression in the corneal epithelium. The methods developed within represent a valid standardized approach that is ideal for screening of a range of delivery formulations.

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“…Attachment of ligands, antibodies, or peptides that bind to specific receptors or proteins is another approach to improve drug efficacy by increasing tumor selectivity and facilitating drug uptake. Liposomes conjugated with cetuximab or trastuzumab, monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) or the human epidermal growth factor receptor 2 (HER2), respectively, reportedly enhanced the cytotoxicity of chemotherapeutic agents encapsulated in liposomes by increasing drug accumulation in targeted tumor tissues 32 – 34 .…”

Section: Discussionmentioning

confidence: 99%

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system

Aoyama

Kuroda

Morihiro

et al. 2017

Sci Rep

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Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40–50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.

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Peptide-mediated Delivery: an Overview of Pathways for Efficient Internalization

Cited by 19 publications

References 159 publications

Efficient therapeutic delivery by a novel cell-permeant peptide derived from KDM4A protein for antitumor and antifibrosis

Efficient therapeutic delivery by a novel cell-permeant peptide derived from KDM4A protein for antitumor and antifibrosis

Effective In Vivo Topical Delivery of siRNA and Gene Silencing in Intact Corneal Epithelium Using a Modified Cell-Penetrating Peptide

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system

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