scholarly journals Internalisation and Biological Activity of Nucleic Acids Delivering Cell-Penetrating Peptide Nanoparticles Is Controlled by the Biomolecular Corona

2021 ◽  
Vol 14 (7) ◽  
pp. 667
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is the formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g., blood stream. In this study, we compared protein corona of CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g., by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be considered while developing delivery systems for nucleic acids.

scholarly journals Internalisation and biological activity of nucleic acids delivering cell-penetrating peptide nanoparticles is controlled by the biomolecular corona

2021 ◽  
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g. blood stream. In this study, we compared CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles, and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g. by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be taken into account while developing delivery systems for nucleic acids.

scholarly journals Delivery of Nucleic Acids and Nanomaterials by Cell-Penetrating Peptides: Opportunities and Challenges

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Yue-Wern Huang ◽  
Han-Jung Lee ◽  
Larry M. Tolliver ◽  
Robert S. Aronstam
Keyword(s):  
Nucleic Acids ◽  
Biomedical Applications ◽  
Cell Penetrating Peptides ◽  
Biologically Active ◽  
The Past ◽  
Cell Penetrating ◽  
Cellular Entry

Many viral and nonviral systems have been developed to aid delivery of biologically active molecules into cells. Among these, cell-penetrating peptides (CPPs) have received increasing attention in the past two decades for biomedical applications. In this review, we focus on opportunities and challenges associated with CPP delivery of nucleic acids and nanomaterials. We first describe the nature of versatile CPPs and their interactions with various types of cargoes. We then discussin vivoandin vitrodelivery of nucleic acids and nanomaterials by CPPs. Studies on the mechanisms of cellular entry and limitations in the methods used are detailed.

scholarly journals Divalent metal ions boost effect of nucleic acids delivered by cell-penetrating peptides

2021 ◽  
Author(s):  
Maria Maloverjan ◽  
Kart Padari ◽  
Aare Abroi ◽  
Ana Rebane ◽  
Margus Pooga
Keyword(s):  
Nucleic Acids ◽  
Therapeutic Potential ◽  
Transfection Efficiency ◽  
Cell Penetrating Peptides ◽  
In Vivo Studies ◽  
Divalent Metal Ions ◽  
Reporter Protein ◽  
Cell Penetrating ◽  
Novel Strategy

Cell-penetrating peptides (CPPs) are promising tools for transfection of various substances, including nucleic acids, into cells. The aim of current work was to search for novel safe and effective approaches for enhancing transfection efficiency of nanoparticles formed of CPP and splice-correcting oligonucleotide (SCO) without increasing the concentration of peptide. We analyzed an effect of inclusion of calcium and magnesium ions into nanoparticles on CPP-mediated transfection in cell culture. We also studied the mechanism of such transfection as well as its efficiency, applicability in case of different cell lines, nucleic acid types and peptides, and possible limitations. We discovered a strong positive effect of these ions on transfection efficiency of SCO, that translated to enhanced synthesis of functional reporter protein. We observed significant changes in intracellular distribution and trafficking of nanoparticles formed with addition of the ions, without increasing cytotoxicity. We propose a novel strategy of preparing CPP-oligonucleotide nanoparticles with enhanced efficiency and, thus, higher therapeutic potential. Our discovery may be translated to primary cell cultures and, possibly, in vivo studies, in the aim to increase CPP-mediated transfection efficiency and likelihood of using CPPs in clinics.

scholarly journals Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery

2020 ◽  
Vol 21 (5) ◽  
pp. 1856
Author(s):  
Qi Shuai ◽  
Yue Cai ◽  
Guangkuo Zhao ◽  
Xuanrong Sun
Keyword(s):  
Cell Penetrating Peptides ◽  
Mice Model ◽  
Block Polymer ◽  
Chemotherapy Drugs ◽  
Tumor Tissues ◽  
Cell Penetrating ◽  
20 Nm ◽  
Targeting Effect

On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7) in vitro. But when further used in vivo, TAT-NP-PTX showed an acceleration of the drug’s plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide’s positive charges may be a hot topic to overcome the present dilemma.

scholarly journals The fate of a designed protein corona on nanoparticles in vitro and in vivo

2015 ◽  
Vol 6 ◽  
pp. 36-46 ◽  
Author(s):  
Denise Bargheer ◽  
Julius Nielsen ◽  
Gabriella Gébel ◽  
Markus Heine ◽  
Sunhild C Salmen ◽  
...  
Keyword(s):  
Superparamagnetic Iron Oxide ◽  
Protein Corona ◽  
Blood Stream ◽  
Minor Importance ◽  
Iron Oxide Particles ◽  
Corona Formation ◽  
The Stability ◽  
Covalently Bound

A variety of monodisperse superparamagnetic iron oxide particles (SPIOs) was designed in which the surface was modified by PEGylation with mono- or bifunctional poly(ethylene oxide)amines (PEG). Using 125I-labeled test proteins (transferrin, albumin), the binding and exchange of corona proteins was studied first in vitro. Incubation with 125I-transferrin showed that with increasing grade of PEGylation the binding was substantially diminished without a difference between simply adsorbed and covalently bound protein. However, after incubation with excess albumin and subsequently whole plasma, transferrin from the preformed transferrin corona was more and more lost from SPIOs in the case of adsorbed proteins. If non-labeled transferrin was used as preformed corona and excess 125I-labeled albumin was added to the reaction mixtures with different SPIOs, a substantial amount of label was bound to the particles with initially adsorbed transferrin but little or even zero with covalently bound transferrin. These in vitro experiments show a clear difference in the stability of a preformed hard corona with adsorbed or covalently bound protein. This difference seems, however, to be of minor importance in vivo when polymer-coated 59Fe-SPIOs with adsorbed or covalently bound 125I-labeled mouse transferrin were injected intravenously in mice. With both protein coronae the 59Fe/125I-labelled particles were cleared from the blood stream within 30 min and appeared in the liver and spleen to a large extent (>90%). In addition, after 2 h already half of the 125I-labeled transferrin from both nanodevices was recycled back into the plasma and into tissue. This study confirms that adsorbed transferrin from a preformed protein corona is efficiently taken up by cells. It is also highlighted that a radiolabelling technique described in this study may be of value to investigate the role of protein corona formation in vivo for the respective nanoparticle uptake.

Hydroxyproline-Based DNA Mimics: A Review on Synthesis and Properties

2006 ◽  
Vol 71 (7) ◽  
pp. 929-955 ◽  
Author(s):  
Vladimir A. Efimov ◽  
Oksana G. Chakhmakhcheva
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Phosphonic Acid ◽  
Peptide Nucleic Acids ◽  
Biological Properties ◽  
High Potential ◽  
Physicochemical And Biological Properties

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.

scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides

Peptides ◽  
2017 ◽  
Vol 87 ◽  
pp. 50-63 ◽  
Author(s):  
Azam Bolhassani ◽  
Behnaz Sadat Jafarzade ◽  
Golnaz Mardani
Keyword(s):  
Therapeutic Proteins ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
In Vivo Delivery

Applications of cell-penetrating peptides in regulation of gene expression

2007 ◽  
Vol 35 (4) ◽  
pp. 770-774 ◽  
Author(s):  
P. Järver ◽  
K. Langel ◽  
S. El-Andaloussi ◽  
Ü. Langel
Keyword(s):  
Gene Expression ◽  
Lipid Bilayers ◽  
Regulation Of Gene Expression ◽  
Cell Penetrating Peptides ◽  
Remarkable Feature ◽  
Cell Penetrating ◽  
Plasmid Delivery ◽  
Interfering Rna

CPPs (cell-penetrating peptides) can be defined as short peptides that are able to efficiently penetrate cellular lipid bilayers. Because of this remarkable feature, they are excellent candidates regarding alterations in gene expression. CPPs have been utilized in in vivo and in vitro experiments as delivery vectors for different bioactive cargoes. This review focuses on the experiments performed in recent years where CPPs have been used as vectors for multiple effectors of gene expression such as oligonucleotides for antisense, siRNA (small interfering RNA) and decoy dsDNA (double-stranded DNA) applications, and as transfection agents for plasmid delivery.

scholarly journals Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study

2007 ◽  
Vol 407 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Samir El-Andaloussi ◽  
Peter Järver ◽  
Henrik J. Johansson ◽  
Ülo Langel
Keyword(s):  
Membrane Integrity ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cargo Delivery ◽  
Wide Range ◽  
Cell Penetrating ◽  
Coupling Strategy ◽  
Transactivator Of Transcription

The use of CPPs (cell-penetrating peptides) as delivery vectors for bioactive molecules has been an emerging field since 1994 when the first CPP, penetratin, was discovered. Since then, several CPPs, including the widely used Tat (transactivator of transcription) peptide, have been developed and utilized to translocate a wide range of compounds across the plasma membrane of cells both in vivo and in vitro. Although the field has emerged as a possible future candidate for drug delivery, little attention has been given to the potential toxic side effects that these peptides might exhibit in cargo delivery. Also, no comprehensive study has been performed to evaluate the relative efficacy of single CPPs to convey different cargos. Therefore we selected three of the major CPPs, penetratin, Tat and transportan 10, and evaluated their ability to deliver commonly used cargos, including fluoresceinyl moiety, double-stranded DNA and proteins (i.e. avidin and streptavidin), and studied their effect on membrane integrity and cell viability. Our results demonstrate the unfeasibility to use the translocation efficacy of fluorescein moiety as a gauge for CPP efficiency, since the delivery properties are dependent on the cargo used. Furthermore, and no less importantly, the toxicity of CPPs depends heavily on peptide concentration, cargo molecule and coupling strategy.

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