NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation

Carreras‐Badosa, Gemma; Maslovskaja, Julia; Periyasamy, Kapilraj; Urgard, Egon; Padari, Kärt; Vaher, Helen; Tserel, Liina; Gestin, Maxime; Kisand, Kai; Arukuusk, Piret; Lou, Chenguang; Langel, Ülo; Wengel, Jesper; Pooga, Margus; Rebane, Ana

doi:10.1016/j.biomaterials.2020.120316

Cited by 33 publications

(27 citation statements)

References 55 publications

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“…This might be one of the main reasons, why CPP-nucleic acid nanoparticles that are highly efficient in vitro, often fail to yield expected outcome in vivo upon systemic administration. Thus, for CPP-mediated transport, transition from bench to bedside, still remains complicated, unless topical delivery is used where less complex protein corona forms around nanoparticles [ 11 , 97 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Thus, for CPPmediated transport, transition from bench to bedside, still remains complicated, unless topical delivery is used where less complex protein corona forms around nanoparticles. 11,96,97 Materials and Methods PF14 (see sequences and characteristics of used CPPs and nucleic acids in Table 1), C22-PF14 and NF55 were purchased from Pepmic (China). Splicing correcting oligonucleotides with 2'OMe modification and phosphorothioate backbone, and labelled with Cy5 or biotin were from Microsynth (Switzerland), or Metabion (Germany), and pGL3 plasmid was from Promega, (4.7 kbp, USA).…”

Section: Discussionmentioning

confidence: 99%

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

Lorents¹,

Maloverjan

Padari³

et al. 2021

Preprint

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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.

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“…NickFect (NF) and PepFect (PF) types of cell‐penetrating peptides were used to deliver miR‐146a, which is a negative regulator of inflammatory response in both tissue‐resident and specialized immune cells. [ 227 ] Both peptides supported the delivery of fluorescently labeled miR‐146a into keratinocytes (KCs) and dendritic cells (DCs). While in case of KCs they were equally effective, the NFs were more efficient in DCs as assessed by measuring downregulation of miR‐146a‐influenced genes.…”

Section: Rna Delivery Applicationsmentioning

confidence: 99%

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

et al. 2021

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In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA‐based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology‐assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in‐depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology‐mediated RNA therapies are discussed.

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NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation

Cited by 33 publications

References 55 publications

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

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

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

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

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