Cell-Penetrating Peptides Selectively Cross the Blood-Brain Barrier In Vivo

Stalmans, Sofie; Bracke, Nathalie; Wynendaele, Evelien; Gevaert, Bert; Peremans, Kathelijne; Burvenich, Christian; Polis, Ingeborgh; Spiegeleer, Bart De

doi:10.1371/journal.pone.0139652

Cited by 174 publications

(176 citation statements)

References 78 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…Among all kinds of cell-penetrating peptides, Tat (YGRKKRRQRRR) is a peptide sequence that presents a relatively high permeability through the blood-brain barrier at 4 µL/(g × min). 13 This remarkable result makes this cell-penetrating peptide a good candidate to combat brain bacterial infections.…”

mentioning

confidence: 99%

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

Garcia¹,

Shi²,

Webster³

2017

IJN

View full text Add to dashboard Cite

Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47–57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat 47–57 ), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae , methicillin-resistant Staphylococcus aureus , and Escherichia coli . Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7–3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood–brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis.

show abstract

mentioning

confidence: 99%

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

Garcia¹,

Shi²,

Webster³

2017

IJN

View full text Add to dashboard Cite

show abstract

“…Thereare several strategiesf or achieving cellular uptake of QDs:n onspecific endocytosis, receptor-mediatede ndocytosis, chemical-mediated transfection (cationic liposomes, translocation peptides, and dendrimers), and mechanical delivery (electroporation and microinjection). [46] However,t he mechanism of delivery is not completely understood;d iffering results have been obtainedw ithd ifferent TATp eptide sequences, different cargosa ttached to the peptide, and different cell types. [37][38][39][40] Endocytosis of QDs and their penetration into organelles entail an umber of problems, and their mechanisms are still under debate.…”

Section: Intracellular Delivery Of Qdsmentioning

confidence: 99%

Quantum Dot‐Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery

2016

View full text Add to dashboard Cite

Quantum dots (QDs) are highly fluorescent nanocrystals with advanced photophysical and spectral properties: high brightness and stability against photobleaching accompanied by broad excitation and narrow emission spectra. Water-soluble QDs functionalized with biomolecules, such as proteins, peptides, antibodies, and drugs, are used for biomedical applications. The advantages of QD-based approaches to immuno-histochemical analysis, single-molecule tracking, and in vivo imaging (over traditional methods with organic dyes and fluorescent proteins) are explained. The unique spectral properties of QDs offer opportunities for designing systems for multiplexed analysis by multicolor imaging for the simultaneous detection of multiple targets. Conjugation of drug molecules with QDs or their incorporation into QD-based drug-delivery particles makes it possible to monitor real-time drug tracking and carry out image-guided therapy. Because of the tunability of their photophysical properties, QDs emitting in the near-infrared have become an attractive tool for deep-tissue mono- and multiphoton in vivo imaging. We review recent achievements in QD applications for bioimaging, targeting, and drug delivery, as well as challenges related to their toxicity and non-biodegradability. Key and perspectives for further development of advanced QD-based nanotools are addressed.

show abstract

“…With the recent application of pVEC to cross the blood brain barrier [338], we believe that this CPP possesses significant potential for drug delivery applications.…”

Section: Pvecmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

Avcı

Akbulut

Özkırımlı

2018

Preprint

View full text Add to dashboard Cite

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide-membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

show abstract

Cell-Penetrating Peptides Selectively Cross the Blood-Brain Barrier In Vivo

Cited by 174 publications

References 78 publications

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

Quantum Dot‐Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery

Membrane Active Peptides and Their Biophysical Characterization

Contact Info

Product

Resources

About