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Article ; Online: Luminescent Assay for the Screening of SARS-CoV-2 M

Sondag, Daan / Merx, Jona / Rossing, Emiel / Boltje, Thomas J / Löwik, Dennis W P M / Nelissen, Frank H T / van Geffen, Mark / van 't Veer, Cornelis / van Heerde, Waander L / Rutjes, Floris P J T

Chembiochem : a European journal of chemical biology

2022 Volume 23, Issue 15, Page(s) e202200190

Abstract: ... globally. The viral chymotrypsin-like main protease (M ...

Abstract	Since the outbreak of SARS-CoV-2 in December 2019 millions of infections have been reported globally. The viral chymotrypsin-like main protease (M
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Coronavirus 3C Proteases ; Cysteine Endopeptidases ; Humans ; Luminescent Measurements ; Molecular Docking Simulation ; Protease Inhibitors/pharmacology ; SARS-CoV-2 ; Viral Nonstructural Proteins
Chemical Substances	Antiviral Agents ; Protease Inhibitors ; Viral Nonstructural Proteins ; Cysteine Endopeptidases (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2022-06-14
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202200190
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Article ; Online: Randomized comparison of near-infrared fluorescence imaging using indocyanine green and 99(m) technetium with or without patent blue for the sentinel lymph node procedure in breast cancer patients.

van der Vorst, Joost R / Schaafsma, Boudewijn E / Verbeek, Floris P R / Hutteman, Merlijn / Mieog, J Sven D / Lowik, Clemens W G M / Liefers, Gerrit-Jan / Frangioni, John V / van de Velde, Cornelis J H / Vahrmeijer, Alexander L

Annals of surgical oncology

2012 Volume 19, Issue 13, Page(s) 4104–4111

Abstract: ... received standard of care using 99(m) technetium-nanocolloid and received 1.6 mL of 500 μM ICG injected ... mapping in breast cancer patients when using NIR fluorescence and 99(m) technetium-nanocolloid. NIR ...

Abstract	Background: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve sentinel lymph node (SLN) mapping of breast cancer. We performed a randomized clinical trial to assess the value of blue dyes when used in combination with NIR fluorescence. We also preliminarily examined the possibility of performing SLN mapping without radiotracers. Methods: Clinical trial subjects were 24 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using 99(m) technetium-nanocolloid and received 1.6 mL of 500 μM ICG injected periareolarly. Patients were randomly assigned to undergo SLN biopsy with or without patent blue. To assess the need for radiocolloids to localize the SLN or SLNs, the surgeon did not use the handheld gamma probe during the first 15 min after the axillary skin incision. Results: SLN mapping was successful in 23 of the 24 patients. No significant difference was found in signal-to-background ratio between the groups with and without patent blue (8.3 ± 3.8 vs. 10.3 ± 5.7, respectively, P = 0.32). In both groups, 100 % of SLNs were radioactive and fluorescent, and in the patent blue group, only 84 % of SLNs were stained blue. In 25 % of patients, the use of the gamma probe was necessary to localize the SLN within the first 15 min. Conclusions: This study shows that there is no benefit of using patent blue for SLN mapping in breast cancer patients when using NIR fluorescence and 99(m) technetium-nanocolloid. NIR fluorescence imaging outperformed patent blue in all patients.
MeSH term(s)	Adult ; Aged ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/pathology ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Ductal, Breast/surgery ; Carcinoma, Lobular/diagnostic imaging ; Carcinoma, Lobular/pathology ; Carcinoma, Lobular/surgery ; Coloring Agents ; Female ; Fluorescence ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted ; Indocyanine Green ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Organotechnetium Compounds ; Prognosis ; Radionuclide Imaging ; Radiopharmaceuticals ; Rosaniline Dyes ; Sentinel Lymph Node Biopsy ; Spectroscopy, Near-Infrared
Chemical Substances	Coloring Agents ; Organotechnetium Compounds ; Radiopharmaceuticals ; Rosaniline Dyes ; sulfan blue (FH1929ICIT) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2012-07-03
Publishing country	United States
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-012-2466-4
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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
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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
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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
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Article ; Online: Bioluminescence imaging on-chip platforms for non-invasive high-content bioimaging.

Araújo-Gomes, Nuno / Zambito, Giorgia / Johnbosco, Castro / Calejo, Isabel / Leijten, Jeroen / Löwik, Clemens / Karperien, Marcel / Mezzanotte, Laura / Teixeira, Liliana Moreira

Biosensors & bioelectronics

2023 Volume 237, Page(s) 115510

Abstract: Incorporating non-invasive biosensing features in organ-on-chip models is of paramount importance for a wider implementation of these advanced in vitro microfluidic platforms. Optical biosensors, based on Bioluminescence Imaging (BLI), enable continuous, ...

Abstract	Incorporating non-invasive biosensing features in organ-on-chip models is of paramount importance for a wider implementation of these advanced in vitro microfluidic platforms. Optical biosensors, based on Bioluminescence Imaging (BLI), enable continuous, non-invasive, and in-situ imaging of cells, tissues or miniaturized organs without the drawbacks of conventional fluorescence imaging. Here, we report the first-of-its-kind integration and optimization of BLI in microfluidic chips, for non-invasive imaging of multiple biological readouts. The cell line HEK293T-GFP was engineered to express NanoLuc® luciferase under the control of a constitutive promoter and were cultured on-chip in 3D, in standard ECM-like hydrogels, to assess optimal cell detection conditions. Using real-time in-vitro dual-color microscopy, Bioluminescence (BL) and fluorescence (FL) were detectable using distinct imaging setups. Detection of the bioluminescent signals were observed at single cell resolution on-chip 20 min post-addition of Furimazine substrate and under perfusion. All hydrogels enabled BLI with higher signal-to-noise ratios as compared to fluorescence. For instance, agarose gels showed a ∼5-fold greater BL signal over background after injection of the substrate as compared to the FL signal. The use of BLI with microfluidic chip technologies opens up the potential for simultaneous in situ detection with continuous monitoring of multicolor cell reporters. Moreover, this can be achieved in a non-invasive manner. BL has great promise as a highly desirable biosensor for studying organ-on-chip platforms.
MeSH term(s)	Humans ; HEK293 Cells ; Biosensing Techniques/methods ; Microfluidics ; Microscopy ; Optical Imaging
Language	English
Publishing date	2023-07-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2023.115510
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Zs.A 2275: Show issues

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Article ; Online: Risk assessment of nutrients: There must be a threshold for their effects.

Löwik, Michiel Rh / Astrup, Arne / Boobis, Alan R / Calder, Philip C / Daniel, Hannelore / Rietjens, Ivonne McM / Sievenpiper, John L / Verhagen, Hans

Regulatory toxicology and pharmacology : RTP

2023 Volume 146, Page(s) 105539

Abstract: Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety ... ...

Abstract	Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be "as low as possible in the context of a nutritionally adequate diet". That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.
MeSH term(s)	Diet ; Nutrients ; Food Safety ; Risk Assessment ; Sugars
Chemical Substances	Sugars
Language	English
Publishing date	2023-12-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604672-1
ISSN	1096-0295 ; 0273-2300
ISSN (online)	1096-0295
ISSN	0273-2300
DOI	10.1016/j.yrtph.2023.105539
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Article ; Online: Novel anti-PD-L1 peptide selected from combinatorial phage library inhibits tumor cell growth and restores T-cell activity.

Tooyserkani, Raheleh / Rasaee, Mohammad Javad / Bandehpour, Mojgan / W P M Löwik, Dennis

Journal of drug targeting

2021 Volume 29, Issue 7, Page(s) 771–782

Abstract: PD-L1 overexpression on tumour cells forms a protective shield against cytotoxic T-cell killing, which consequently leads to immune evasion. Engagement of PD-1 in tumour infiltrating T cells with PD-L1 results in an exhausted T-cell phenotype, thus ... ...

Abstract	PD-L1 overexpression on tumour cells forms a protective shield against cytotoxic T-cell killing, which consequently leads to immune evasion. Engagement of PD-1 in tumour infiltrating T cells with PD-L1 results in an exhausted T-cell phenotype, thus preventing an effective immune response against tumour cells. In the present study, we employed phage display combinatorial peptide library to discover anti-PD-L1 peptides. The peptides discovered here, could computationally exhibit specific interactions with PD-L1 at residues with which PD-1 also interacts. Binding affinity and specificity of the peptides were examined by flow cytometry. Anti- tumour activity of peptides was also investigated using several cell-based assays. Surprisingly, we demonstrated that Pep-39 can inhibit PDL-1, and reduce MDA-MB-231, CT-26, and DU-145 cells survival. In co-culture experiments, Pep-39 restored proliferation of Jurkat cells cultured in the presence of MDA-MB-231 cells. In addition, Jurkat cells apoptosis was impeded, indicating blocking potential of Pep-39 against PD-1/PD-L1 interaction.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Flow Cytometry ; Humans ; Jurkat Cells ; Mice ; Neoplasms/drug therapy ; Neoplasms/pathology ; Peptide Library ; Peptides/chemistry ; Peptides/pharmacology
Chemical Substances	Antineoplastic Agents ; B7-H1 Antigen ; CD274 protein, human ; Peptide Library ; Peptides
Language	English
Publishing date	2021-07-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1187110-6
ISSN	1029-2330 ; 1061-186X
ISSN (online)	1029-2330
ISSN	1061-186X
DOI	10.1080/1061186X.2021.1879087
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Article: Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain.

Stroet, Marcus C M / de Blois, Erik / de Jong, Marion / Seimbille, Yann / Mezzanotte, Laura / Löwik, Clemens W G M / Panth, Kranthi M

Cancers

2022 Volume 14, Issue 4

Abstract: Purpose: To assess our improved NACA for the detection of tumor necrosis.: Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive ... ...

Abstract	Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [ Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [ Conclusions: Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging.
Language	English
Publishing date	2022-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14040861
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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
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