Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Freimann, Krista; Arukuusk, Piret; Kurrikoff, Kaido; Pärnaste, Ly; Raid, Raivo; Piirsoo, Andres; Pooga, Margus; Langel, Ülo

doi:10.1016/j.omtn.2017.10.011

Cited by 29 publications

(19 citation statements)

References 16 publications

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“…In this line, stearyl-TP10 increased DNA delivery in different cell lines as similar to lipofection [216]. Effective stearylated Transportan analogues termed as NickFects (NF) were designed to improve DNA transfection efficacy because of long shelf-life, lack of aggregation after reconstitution, high stability against enzymatic degradation, and higher bioactivity in vivo [138,217]. Also, the modified CPPs with cysteine could improve their properties.…”

Section: Nucleic Acid Deliverymentioning

confidence: 99%

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Kardani

Milani

Shabani

et al. 2019

Expert Opinion on Drug Delivery

152

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Introduction: Cell penetrating peptides (CPPs) known as protein translocation domains (PTD), membrane translocating sequences (MTS), or Trojan peptides (TP) are able to cross biological membranes without clear toxicity using different mechanisms, and facilitate the intracellular delivery of a variety of bioactive cargos. CPPs could overcome some limitations of drug delivery and combat resistant strains against a broad range of diseases. Despite delivery of different therapeutic molecules by CPPs, they lack cell specificity and have a short duration of action. These limitations led to design of combined cargo delivery systems and subsequently improvement of their clinical applications. Areas covered: This review covers all our studies and other researchers in different aspects of CPPs such as classification, uptake mechanisms, and biomedical applications. Expert opinion: Due to low cytotoxicity of CPPs as compared to other carriers and final degradation to amino acids, they are suitable for preclinical and clinical studies. Generally, the efficiency of CPPs was suitable to penetrate the cell membrane and deliver different cargos to specific intracellular sites. However, no CPP-based therapeutic approach has approved by FDA, yet; because there are some disadvantages for CPPs including short half-life in blood, and nonspecific CPP-mediated delivery to normal tissue. Thus, some methods were used to develop the functions of CPPs in vitro and in vivo including the augmentation of cell specificity by activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, incorporation of CPPs into multifunctional dendrimeric or liposomal nanocarriers to improve selectivity and efficiency especially in tumor cells.

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Section: Nucleic Acid Deliverymentioning

confidence: 99%

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Kardani

Milani

Shabani

et al. 2019

Expert Opinion on Drug Delivery

152

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“…RNA interference (RNAi) [ 181 – 183 ], CRISPR/Cas9 editing [ 55 ], plasmid transfection [ 184 ], and lentiviral vector infection [ 185 ] are methods that can be used to decrease or increase circRNA levels. Additionally, nanoparticles can be loaded with exogenous circRNAs and used to carry them for targeted therapy [ 186 ] (Fig. 5 ).…”

Section: Introductionmentioning

confidence: 99%

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer

et al. 2021

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Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5′ caps and 3′ poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients’ survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

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“…Analysed particles contained plasmid DNA (pDNA) or splice-correcting oligonucleotide (SCO) that were non-covalently complexed with three CPPs: PepFect 14 (PF14), PF14 modified with a 22-carbon fatty acid tail (C22-PF14) 56 or NickFect 55 (NF55). 57 We studied the formation of protein corona on different nanoparticles in bovine serum as a representative of cell culture systems, in murine serum as a typical animal model used in the development and testing of such nanoparticles, and in human serum as a representative of the actual target for drug development (Schema 1). We observed that dissimilar protein corona forming in different sera translates to unequal uptake of studied nanoparticles by cultured cells, and varying biological response to nucleic acid cargo.…”

Section: Introductionmentioning

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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Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Cited by 29 publications

References 16 publications

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer

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

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