The World of Cell Penetrating: the Future of Medical Applications

Falanga, Annarita; Lombardi, Lucia; Galdiero, Emilia; Genio, Valentina Del; Galdiero, Stefania

doi:10.4155/fmc-2020-0140

Cited by 23 publications

(26 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this aim, micelles, polymers, lipid-and peptide-based nanoparticles are among the most studied systems for gene release [25][26][27][28]. In particular, cell-penetrating peptides (CPP) offer exceptional properties to be explored as gene delivery vehicles for successful gene therapy [28][29][30][31][32]. CPPs are short peptides, usually of fewer than 30 amino acids, and can be separated into arginine-rich and amphipathic peptides.…”

Section: Introductionmentioning

confidence: 99%

“…However, the exact mechanism CPPs use to penetrate cells is still not fully understood, with endocytosis and direct penetration being the most probable hypothesis [30,33]. Despite this fact, their great potential in conjugation with therapeutic molecules and in their cellular internalization has been well recognized, leading to the significant participation of CCPs in biomedical applications [31][32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

et al. 2021

View full text Add to dashboard Cite

A mitochondrion is a cellular organelle able to produce cellular energy in the form of adenosine triphosphate (ATP). As in the nucleus, mitochondria contain their own genome: the mitochondrial DNA (mtDNA). This genome is particularly susceptible to mutations that are at the basis of a multitude of disorders, especially those affecting the heart, the central nervous system and muscles. Conventional clinical practice applied to mitochondrial diseases is very limited and ineffective; a clear need for innovative therapies is demonstrated. Gene therapy seems to be a promising approach. The use of mitochondrial DNA as a therapeutic, optimized by peptide-based complexes with mitochondrial targeting, can be seen as a powerful tool in the reestablishment of normal mitochondrial function. In line with this requirement, in this work and for the first time, a mitochondrial-targeting sequence (MTS) has been incorporated into previously researched peptides, to confer on them a targeting ability. These peptides were then considered to complex a plasmid DNA (pDNA) which contains the mitochondrial gene ND1 (mitochondrially encoded NADH dehydrogenase 1 protein), aiming at the formation of peptide-based nanoparticles. Currently, the ND1 plasmid is one of the most advanced bioengineered vectors for conducting research on mitochondrial gene expression. The formed complexes were characterized in terms of pDNA complexation capacity, morphology, size, surface charge and cytotoxic profile. These data revealed that the developed carriers possess suitable properties for pDNA delivery. Furthermore, in vitro studies illustrated the mitochondrial targeting ability of the novel peptide/pDNA complexes. A comparison between the different complexes revealed the most promising ones that complex pDNA and target mitochondria. This may contribute to the optimization of peptide-based non-viral systems to target mitochondria, instigating progress in mitochondrial gene therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In general, the transmembrane pathways of CPPs include direct penetration and endocytosis [ 23 , 24 ]; they depend on the type of target cells [ 47 ], the cargo carried and the physicochemical properties of the penetrating peptide sequence [ 48 ]. Although Bouquier et al ., [ 49 ] proved that ACPP-TAMRA enters hippocampal neurons through endocytosis, the ACPP used in our experiment [ 28 ] is different from ACPP-TAMRA [ 49 ] in the peptide sequence composition of the linker, so the membrane penetration mechanism of the ACPP used in our experiment is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Cell-penetrating peptides (CPPs) are peptides with effective intracellular delivery performance, low cytotoxicity and low immunogenicity [ 23 , 24 ]. These molecules can carry a variety of proteins into the cell, such as Rp3 (13.29 kDa) [ 25 ] and CARM1 (66.89 kDa) [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human lung cancer cells by anti-p21Ras scFv mediated by the activatable cell-penetrating peptide

Lin

Feng³

et al. 2021

Anti-Cancer Drugs

View full text Add to dashboard Cite

Activatable cell-penetrating peptide (ACPP) is a tumour-targeting cell-penetrating peptide. Here, we used ACPP to carry anti-p21Ras scFv for Ras-driven cancer therapy. The ACPP-p21Ras scFv fusion protein was prepared by a prokaryotic expression system and Ni-NTA column purification. The human tumour cell lines A549, SW480, U251 and Huh7 and the normal cell line BEAS 2B were used to study the tumor-targeting and membrane-penetrating ability of ACPP-p21Ras scFv. The antitumour activity of ACPP-p21Ras scFv on A549 cells and H1299 cells in vitro was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, scratch wound healing, plate cloning and apoptosis assays. The penetration pathway of ACPP was determined by enhanced green fluorescent protein. The ACPP-p21Ras scFv fusion protein was successfully obtained at a concentration of 1.8 mg/ml. We found that ACPP-p21Ras scFv could penetrate tumour cell membranes with high expression of matrix metalloproteinase-2 (MMP-2), effectively inhibit the migration and proliferation of A549 cells and H1299 cells, and promote the apoptosis of A549 cells and H1299 cells. The membrane penetration experiment demonstrated that ACPP could enter A549 cells by direct penetration. The ability of ACPP to penetrate the membrane was affected by the addition of a membrane affinity inhibitor and a change in the potential difference across the cell membrane but not by the addition of endocytosis inhibitors and a change in temperature. The ACPP-p21Ras scFv fusion protein can penetrate tumour cells with MMP-2 expression and has antitumour activity against A549 cells and H1299 cells in vitro . This molecule is expected to become a potential antitumour drug for Ras gene-driven lung cancer.

show abstract

“…Since then, plenty of different CPPs capable to transport diverse cargos across cellular membranes have been published and outlined in numerous comprehensive reviews. (Koren and Torchilin, 2012;Copolovici et al, 2014;Guidotti et al, 2017;Kalafatovic and Giralt, 2017;Taylor and Zahid, 2020;Falanga et al, 2020;Desale et al, 2021) Although a lot of research is focused on CPPs, some questions remain open. As an example, the uptake mechanism of these molecular transporters is still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Cyclic Peptoid-Peptide Hybrids as Versatile Molecular Transporters

et al. 2021

View full text Add to dashboard Cite

Addressing intracellular targets is a challenging task that requires potent molecular transporters capable to deliver various cargos. Herein, we report the synthesis of hydrophobic macrocycles composed of both amino acids and peptoid monomers. The cyclic tetramers and hexamers were assembled in a modular approach using solid as well as solution phase techniques. To monitor their intracellular localization, the macrocycles were attached to the fluorophore Rhodamine B. Most molecular transporters were efficiently internalized by HeLa cells and revealed a specific accumulation in mitochondria without the need for cationic charges. The data will serve as a starting point for the design of further cyclic peptoid-peptide hybrids presenting a new class of highly efficient, versatile molecular transporters.

show abstract

The World of Cell Penetrating: the Future of Medical Applications

Cited by 23 publications

References 129 publications

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

Inhibition of human lung cancer cells by anti-p21Ras scFv mediated by the activatable cell-penetrating peptide

Cyclic Peptoid-Peptide Hybrids as Versatile Molecular Transporters

Contact Info

Product

Resources

About