High-content screening of peptide-based non-viral gene delivery systems

Raad, Markus de; Teunissen, Erik A.; Lelieveld, Daphne; Egan, David A.; Mastrobattista, Enrico

doi:10.1016/j.jconrel.2011.09.078

Cited by 21 publications

(26 citation statements)

References 36 publications

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“…Nevertheless, encapsulation properties of such amino acid-based materials may allow their use as drug and gene delivery vehicles. [39] In this respect, proven polymersomes concepts, such as targeting, may also lead to a fast development of advanced peptosomes. [40,41] Peptide Beads Peptide beads are spherical particles in the submicrometer range, formed by self-assembly of the amphiphilic peptide Ac-X 3 -gT and its close analogues AcC-X 3 -gT, AcC(sl)-X 3 -gT, and Ac-X 3 -gT-C. [13,14] To obtain information about the underlying structure and formation process, we extensively characterized the beads by microscopic and light scattering (LS) techniques, such as AFM, TEM, SEM, SLS and DLS.…”

Section: Micelles and Fibersmentioning

confidence: 99%

Self-assembled Structures from Amphiphilic Peptides

Sigg¹,

Schuster²,

Meier

2013

Chimia

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Nanotechnology and its applications are strongly influenced by structures self-assembled from a variety of different materials. This review covers nanostructures, including micelles, rod-like micelles, fibers and peptide beads, self-assembled from de novo designed amphiphilic peptides. The latter are promising candidates for the development of nanoscale carrier systems because they are completely composed of amino acids. In addition to designing primary sequences, secondary structure and external parameters are also discussed with respect to their impact on self-assembly. Moreover, the assembly process itself is examined. Potential applications range from gene and drug delivery devices to diagnostics, thereby highlighting the versatility of the system.

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Section: Micelles and Fibersmentioning

confidence: 99%

Self-assembled Structures from Amphiphilic Peptides

Sigg¹,

Schuster²,

Meier

2013

Chimia

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“…32, 45–47 Although reports suggest low molecular weight polyarginine/pDNA complexes may achieve modest transfection with negligible cytotoxicity, the large particle size (microparticles) is a limitation. 32 Indeed, high molecular weight polycations often have the ability to condense DNA into small and stable complexes while low molecular weight polycations often yield large and unstable complexes.…”

Section: Introductionmentioning

confidence: 99%

Polyarginine Molecular Weight Determines Transfection Efficiency of Calcium Condensed Complexes

Alhakamy

Berkland

2013

Mol. Pharmaceutics

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Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression, but poses a risk of increased cytotoxicity and immunogenicity compared to low molecular weight CCPs. Conversely, low molecular weight CPPs typically have low transfection efficiency due to large complex size. Complexes made using low molecular weight CPPs were found to be condensed to a small size by adding calcium. In this study, complexes of low molecular weight polyarginine and pDNA were condensed with calcium. These complexes showed high transfection efficiency and low cytotoxicity in A549 carcinomic human alveolar basal epithelial cells. The relationship between transfection efficiency and polyarginine size (5, 7, 9 or 11 amino acids), polyarginine/pDNA charge ratios, and calcium concentrations were studied. Polyarginine 7 was significantly more effective than other polyarginines under most formulation conditions suggesting a link between cell penetration ability and transfection efficiency.

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“…Data from different studies had already shown that the 70 vectors could transfect multiple cell types, but complicating factors included a range of different incubation times and the presence or absence of serum, making head-to-head comparisons impossible. Therefore, HCA assessment [76] enabled standardization of the protocol for transfection in a single cell type in serum-containing medium over a 4-h incubation, followed by expression analysis after 48 h, thereby enabling rapid, reliable, comprehensive comparisons of the 70 peptides. Of note was that only five out of 70 peptides had high levels of transfection efficiency and it seemed that weak transfection capacity for the majority related to the presence of serum, which is often not included in transfection media in vitro, but which is highly relevant in vivo.…”

Section: Hca: Particulate Delivery To Access Intracellular Targetsmentioning

confidence: 99%

“…Recent reports have identified how HCA could provide a potential solution to this problem by enabling libraries of NPs to be screened in parallel for specific biomedical applications, resulting in the rapid identification of lead delivery systems. For example, HCA was used to screen a library of 70 peptide-based gene delivery vectors for the delivery of plasmid (p)DNA into COS-7 cells [76]. These parameters included cytotoxicity and transfection efficiency in nondividing cells.…”

mentioning

confidence: 99%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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High-content screening of peptide-based non-viral gene delivery systems

Cited by 21 publications

References 36 publications

Self-assembled Structures from Amphiphilic Peptides

Self-assembled Structures from Amphiphilic Peptides

Polyarginine Molecular Weight Determines Transfection Efficiency of Calcium Condensed Complexes

High-content analysis for drug delivery and nanoparticle applications

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