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  1. Article ; Online: Dodging Endosomes: Effective Cytosolic Antibody Delivery.

    Löwik, Dennis W P M

    Chembiochem : a European journal of chemical biology

    2017  Volume 18, Issue 22, Page(s) 2196–2198

    Abstract: On the inside: New methodologies for delivering antibodies right into the cytosol of cells either directly across the plasma membrane or by allowing the antibody to escape from endosomes have been proposed recently by the Cardoso/Hackenberger and Futaki ... ...

    Abstract On the inside: New methodologies for delivering antibodies right into the cytosol of cells either directly across the plasma membrane or by allowing the antibody to escape from endosomes have been proposed recently by the Cardoso/Hackenberger and Futaki groups, respectively.
    Language English
    Publishing date 2017-11-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.201700510
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade.

    Shoari, Alireza / Tooyserkani, Raheleh / Tahmasebi, Mehdi / Löwik, Dennis W P M

    Pharmaceutics

    2021  Volume 13, Issue 9

    Abstract: Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse amino acid sequences with the ability to cross cellular membranes. CPPs can deliver several bioactive cargos, including proteins, peptides, nucleic acids ...

    Abstract Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse amino acid sequences with the ability to cross cellular membranes. CPPs can deliver several bioactive cargos, including proteins, peptides, nucleic acids and chemotherapeutics, into cells. Ever since their discovery, synthetic and natural CPPs have been utilized in therapeutics delivery, gene editing and cell imaging in fundamental research and clinical experiments. Over the years, CPPs have gained significant attention due to their low cytotoxicity and high transduction efficacy. In the last decade, multiple investigations demonstrated the potential of CPPs as carriers for the delivery of therapeutics to treat various types of cancer. Besides their remarkable efficacy owing to fast and efficient delivery, a crucial benefit of CPP-based cancer treatments is delivering anticancer agents selectively, rather than mediating toxicities toward normal tissues. To obtain a higher therapeutic index and to improve cell and tissue selectivity, CPP-cargo constructions can also be complexed with other agents such as nanocarriers and liposomes to obtain encouraging outcomes. This review summarizes various types of CPPs conjugated to anticancer cargos. Furthermore, we present a brief history of CPP utilization as delivery systems for anticancer agents in the last decade and evaluate several reports on the applications of CPPs in basic research and preclinical studies.
    Language English
    Publishing date 2021-09-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics13091391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Activation of cell-penetrating peptide fragments by disulfide formation.

    Tooyserkani, Raheleh / Lipiński, Wojciech / Willemsen, Bob / Löwik, Dennis W P M

    Amino acids

    2020  Volume 52, Issue 8, Page(s) 1161–1168

    Abstract: Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative ...

    Abstract Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative analysis. After disulfide formation between two complementary CPP fragments, cellular uptake of the resulting conjugates was observed. As confirmed by in vitro experiments, the conjugated peptides showed uptake activity comparable to the native CPP sequences, while the truncated peptides were hardly active. Until now, this split CPP strategy has only been demonstrated for oligo-arginine CPPs, but here we demonstrate that it is also applicable to other cell-penetrating peptides. This wider applicability may help in the design of new activatable cell-penetrating peptides for, e.g., targeted drug delivery.
    MeSH term(s) Cell-Penetrating Peptides/chemistry ; Disulfides/chemistry ; Fluoresceins/chemistry ; HeLa Cells ; Humans ; Microscopy, Fluorescence/methods ; Peptide Fragments/chemistry ; Peptides/chemistry ; tat Gene Products, Human Immunodeficiency Virus/chemistry
    Chemical Substances Cell-Penetrating Peptides ; Disulfides ; Fluoresceins ; Pep-3 peptide ; Peptide Fragments ; Peptides ; tat Gene Products, Human Immunodeficiency Virus ; tat peptide (49-57), Human immunodeficiency virus 1 ; 6-carboxyfluorescein (3301-79-9) ; penetratin (A2AQZ20TEK)
    Language English
    Publishing date 2020-07-31
    Publishing country Austria
    Document type Journal Article
    ZDB-ID 1121341-3
    ISSN 1438-2199 ; 0939-4451
    ISSN (online) 1438-2199
    ISSN 0939-4451
    DOI 10.1007/s00726-020-02880-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Activatable cell-penetrating peptides: 15 years of research.

    de Jong, Heleen / Bonger, Kimberly M / Löwik, Dennis W P M

    RSC chemical biology

    2020  Volume 1, Issue 4, Page(s) 192–203

    Abstract: An important hurdle for the intracellular delivery of large cargo is the cellular membrane, which protects the cell from exogenous substances. Cell-penetrating peptides (CPPs) can cross this barrier but their use as drug delivery vehicles is hampered by ... ...

    Abstract An important hurdle for the intracellular delivery of large cargo is the cellular membrane, which protects the cell from exogenous substances. Cell-penetrating peptides (CPPs) can cross this barrier but their use as drug delivery vehicles is hampered by their lack of cell type specificity. Over the past years, several approaches have been explored to control the activity of CPPs that can be primed for cellular uptake. Since the first report on such activatable CPPs (ACPPs) in 2004, various methods of activation have been developed. Here, we provide an overview of the different ACPPs strategies known to date and summarize the benefits, drawbacks, and future directions.
    Language English
    Publishing date 2020-08-26
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2633-0679
    ISSN (online) 2633-0679
    DOI 10.1039/d0cb00114g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Activation of cell-penetrating peptide fragments by disulfide formation

    Tooyserkani, Raheleh / Lipiński, Wojciech / Willemsen, Bob / Löwik, Dennis W. P. M

    Amino acids. 2020 Aug., v. 52, no. 8

    2020  

    Abstract: Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative ...

    Abstract Three cell-penetrating peptides (CPPs), Tat, Pep-3 and penetratin, were split into two parts and each fragment was terminated with a cysteine residue, to allow disulfide bridge formation, as well as a fluorescent label, for visualization and quantitative analysis. After disulfide formation between two complementary CPP fragments, cellular uptake of the resulting conjugates was observed. As confirmed by in vitro experiments, the conjugated peptides showed uptake activity comparable to the native CPP sequences, while the truncated peptides were hardly active. Until now, this split CPP strategy has only been demonstrated for oligo-arginine CPPs, but here we demonstrate that it is also applicable to other cell-penetrating peptides. This wider applicability may help in the design of new activatable cell-penetrating peptides for, e.g., targeted drug delivery.
    Keywords cysteine ; disulfide bonds ; disulfides ; drugs ; fluorescence ; peptides ; quantitative analysis
    Language English
    Dates of publication 2020-08
    Size p. 1161-1168.
    Publishing place Springer Vienna
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 1121341-3
    ISSN 1438-2199 ; 0939-4451
    ISSN (online) 1438-2199
    ISSN 0939-4451
    DOI 10.1007/s00726-020-02880-x
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Comparison of Bioorthogonally Cross-Linked Hydrogels for

    Zhan, Henan / de Jong, Heleen / Löwik, Dennis W P M

    ACS applied bio materials

    2019  Volume 2, Issue 7, Page(s) 2862–2871

    Abstract: Hydrogels are water-saturated polymer networks and extensively used in drug delivery, tissue repair engineering, and cell cultures. For encapsulation of drugs or cells, the possibility to form ... ...

    Abstract Hydrogels are water-saturated polymer networks and extensively used in drug delivery, tissue repair engineering, and cell cultures. For encapsulation of drugs or cells, the possibility to form hydrogels
    Language English
    Publishing date 2019-06-28
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.9b00253
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Self-recovering dual cross-linked hydrogels based on bioorthogonal click chemistry and ionic interactions.

    Zhan, Henan / Jiang, Shanshan / Jonker, Anika M / Pijpers, Imke A B / Löwik, Dennis W P M

    Journal of materials chemistry. B

    2020  Volume 8, Issue 27, Page(s) 5912–5920

    Abstract: The biocompatible, injectable and high water-swollen nature of hydrogels makes them a popular candidate to imitate the extracellular matrix (ECM) for tissue engineering both in vitro and in vivo. However, commonly used covalently cross-linked hydrogels, ... ...

    Abstract The biocompatible, injectable and high water-swollen nature of hydrogels makes them a popular candidate to imitate the extracellular matrix (ECM) for tissue engineering both in vitro and in vivo. However, commonly used covalently cross-linked hydrogels, despite their stability and tunability, are elastic and deteriorate as bulk material degrades which would impair proper cell function. To improve these deficiencies, here, we present a self-recovering cross-linked hydrogel formed instantaneously with functionalized poly(ethylene glycol) as a basis. We combine covalent cross-links introduced via a strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction and non-covalent links between phosphonate groups and calcium ions. By adjusting the ratios of non-covalent and covalent cross-links, we synthesized these dual cross-linked (DC) hydrogels that displayed storage moduli below ∼2000 Pa and relaxation times from seconds to minutes. The gels recovered to 41-96% of their initial mechanical properties after two subsequent strain failures. Cryo-scanning electron microscopy revealed that DC hydrogels containing approximately equal amounts of covalent and non-covalent cross-links displayed phase separation. Finally, we functionalized the DC hydrogels by incorporating an integrin binding motif, RGDS, to provide a biocompatible environment for human mesenchymal stem cells (HMSCs) by facilitating adhesion inside the gel network. Inside these DC gels HSMCs displayed a viability up to 73% after five days of cell culture.
    MeSH term(s) Alkynes/chemistry ; Azides/chemistry ; Biocompatible Materials/chemistry ; Biocompatible Materials/metabolism ; Calcium/chemistry ; Cations, Divalent/chemistry ; Cell Proliferation ; Cells, Cultured ; Click Chemistry ; Cross-Linking Reagents/chemistry ; Cycloaddition Reaction ; Extracellular Matrix/metabolism ; Humans ; Hydrogels/chemistry ; Hydrogels/metabolism ; Mechanical Phenomena ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Oligopeptides/chemistry ; Organophosphonates/chemistry ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/metabolism ; Rheology ; Tissue Engineering ; Tissue Scaffolds/chemistry
    Chemical Substances Alkynes ; Azides ; Biocompatible Materials ; Cations, Divalent ; Cross-Linking Reagents ; Hydrogels ; Oligopeptides ; Organophosphonates ; Polyethylene Glycols (3WJQ0SDW1A) ; arginyl-glycyl-aspartyl-serine (AC6UDA2MFC) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-06-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2702241-9
    ISSN 2050-7518 ; 2050-750X
    ISSN (online) 2050-7518
    ISSN 2050-750X
    DOI 10.1039/d0tb01042a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Activity Sensing of Coagulation and Fibrinolytic Proteases.

    Sondag, Daan / Verhoeven, Stijn / Löwik, Dennis W P M / van Geffen, Mark / Veer, Cornelis Van't / van Heerde, Waander L / Boltje, Thomas J / Rutjes, Floris P J T

    Chemistry (Weinheim an der Bergstrasse, Germany)

    2023  Volume 29, Issue 18, Page(s) e202203473

    Abstract: The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity ... ...

    Abstract The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity can lead to life-threatening bleeding disorders and thrombosis. This review summarizes the essential proteases involved in blood coagulation and fibrinolysis, the endogenous peptide sequences they recognize and hydrolyze, and synthetic peptide probes based on these sequences to measure their activity. The information in this review can contribute to developing novel anticoagulant therapies and specific substrates for point-of-care diagnosis of coagulation pathologies.
    MeSH term(s) Humans ; Blood Coagulation ; Fibrinolysis/physiology ; Thrombosis ; Serine Proteases ; Serine Endopeptidases
    Chemical Substances Serine Proteases (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2023-02-07
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1478547-X
    ISSN 1521-3765 ; 0947-6539
    ISSN (online) 1521-3765
    ISSN 0947-6539
    DOI 10.1002/chem.202203473
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Solid-Phase Synthesis of Caged Luminescent Peptides via Side Chain Anchoring.

    Sondag, Daan / Heming, Jurriaan J A / Löwik, Dennis W P M / Krivosheeva, Elena / Lejeune, Denise / van Geffen, Mark / Van't Veer, Cornelis / van Heerde, Waander L / Beens, Marjolijn C J / Kuijpers, Brian H M / Boltje, Thomas J / Rutjes, Floris P J T

    Bioconjugate chemistry

    2023  Volume 34, Issue 12, Page(s) 2234–2242

    Abstract: The synthesis of caged luminescent peptide substrates remains challenging, especially when libraries of the substrates are required. Most currently available synthetic methods rely on a solution-phase approach, which is less suited for parallel synthesis ...

    Abstract The synthesis of caged luminescent peptide substrates remains challenging, especially when libraries of the substrates are required. Most currently available synthetic methods rely on a solution-phase approach, which is less suited for parallel synthesis purposes. We herein present a solid-phase peptide synthesis (SPPS) method for the synthesis of caged aminoluciferin peptides via side chain anchoring of the P
    MeSH term(s) Solid-Phase Synthesis Techniques ; Peptides/chemistry ; Peptide Library ; Lysine/chemistry ; Arginine
    Chemical Substances Peptides ; Peptide Library ; Lysine (K3Z4F929H6) ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2023-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1024041-x
    ISSN 1520-4812 ; 1043-1802
    ISSN (online) 1520-4812
    ISSN 1043-1802
    DOI 10.1021/acs.bioconjchem.3c00381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Theranostic PSMA ligands with optimized backbones for intraoperative multimodal imaging and photodynamic therapy of prostate cancer.

    Derks, Yvonne H W / van Lith, Sanne A M / Amatdjais-Groenen, Helene I V / Wouters, Lieke W M / Kip, Annemarie / Franssen, Gerben M / Laverman, Peter / Löwik, Dennis W P M / Heskamp, Sandra / Rijpkema, Mark

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 7, Page(s) 2425–2435

    Abstract: Introduction: The first generation ligands for prostate-specific membrane antigen (PSMA)-targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we ... ...

    Abstract Introduction: The first generation ligands for prostate-specific membrane antigen (PSMA)-targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA ligands by crucial modification of existing PSMA ligand backbone structures (PSMA-1007/PSMA-617) for multimodal imaging and targeted PDT of PCa.
    Methods: Various new PSMA ligands were synthesized using solid-phase chemistry and provided with a DOTA chelator for
    Results: In order to synthesize the new dual-labeled ligands, we modified the PSMA peptide linker by substitution of a glutamic acid into a lysine residue, providing a handle for conjugation of multiple functional moieties. Ligand optimization showed that the new backbone structure leads to high-affinity PSMA ligands (all IC
    Conclusion: The new high-affinity dual-labeled PSMA-targeting ligands with optimized backbone compositions showed increased tumor targeting and enabled multimodal image-guided PCa surgery combined with targeted photodynamic therapy.
    MeSH term(s) Animals ; Antigens, Surface/metabolism ; Cell Line, Tumor ; Glutamate Carboxypeptidase II/metabolism ; Humans ; Ligands ; Male ; Mice ; Mice, Nude ; Multimodal Imaging ; Photochemotherapy ; Photosensitizing Agents/therapeutic use ; Precision Medicine ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/therapy ; Tissue Distribution
    Chemical Substances Antigens, Surface ; Ligands ; Photosensitizing Agents ; Glutamate Carboxypeptidase II (EC 3.4.17.21)
    Language English
    Publishing date 2022-01-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-022-05685-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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