Monika Schäfer-Korting’s research while affiliated with Freie Universität Berlin and other places

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Publications (165)


Looking to the Future: Drug Delivery and Targeting in the Prophylaxis and Therapy of Severe and Chronic Diseases
  • Chapter

October 2023

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10 Reads

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2 Citations

Handbook of Experimental Pharmacology

Monika Schäfer-Korting

High molecular weight actives and cell-based therapy have the potential to revolutionize the prophylaxis and therapy of severe diseases. Yet, the size and nature of the agents – proteins, nucleic acids, cells – challenge drug delivery and thus formulation development. Moreover, off-target effects may result in severe adverse drug reactions. This makes delivery and targeting an essential component of high-end drug development. Loading to nanoparticles facilitates delivery and enables targeted mRNA vaccines and tumor therapeutics. Stem cell therapy opens up a new horizon in diabetes type 1 among other domains which may enhance the quality of life and life expectancy. Cell encapsulation protects transplants against the recipient’s immune system, may ensure long-term efficacy, avoid severe adverse reactions, and simplify the management of rare and fatal diseases. The knowledge gained so far encourages to widen the spectrum of potential indications. Co-development of the active agent and the vehicle has the potential to accelerate drug research. One recommended starting point is the use of computational approaches. Transferability of preclinical data to humans will benefit from performing studies first on validated human 3D disease models reflecting the target tissue, followed by studies on validated animal models. This makes approaching a new level in drug development a multidisciplinary but ultimately worthwhile and attainable challenge. Intense monitoring of the patients after drug approval and periodic reporting to physicians and scientists remain essential for the safe use of drugs especially in rare diseases and pave future research.


Preclinical Testing of Dendritic Core–Multishell Nanoparticles in Inflammatory Skin Equivalents

March 2022

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76 Reads

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4 Citations

Molecular Pharmaceutics

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Human skin equivalents emerged as novel tools in preclinical dermatological research. It is being claimed that they may bridge the translational gap between preclinical and clinical research, yet only a few studies have investigated their suitability for preclinical drug testing so far. Therefore, we investigated if inflammatory skin equivalents, which emulate hallmarks of atopic dermatitis (AD), are suitable to assess the anti-inflammatory effects of dexamethasone (DXM) in a cream formulation or loaded onto dendritic core-multishell nanoparticles. Topical DXM application resulted in significantly decreased expression of the proinflammatory cytokine TSLP, increased expression of the skin barrier protein involucrin, and facilitated glucocorticoid receptor translocation in a dose-dependent manner. Further, DXM treatment inhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effects of glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of the nanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful study design.


Correction to: Solvent Effects on Skin Penetration and Spatial Distribution of the Hydrophilic Nitroxide Spin Probe PCA Investigated by EPR
  • Article
  • Full-text available

March 2022

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49 Reads

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1 Citation

Cell Biochemistry and Biophysics

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Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery

October 2021

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29 Reads

The improved understanding of disease pathways enables the identification of relevant pharmacological targets and the development of drugs addressing these targets. Although a great deal of the focus for active targeted nanotechnology has been on anti-cancer drugs, the need for active targeting nanotechnology and the same translational gap applies to many other diseases. Nanotechnology for topical and cutaneous delivery faces similar challenges with a vast array of technological improvements, but few marketed products. This chapter describes the pathophysiology and treatment of some common skin conditions. Reconstructed human skin is generated from isolated juvenile human keratinocytes and fibroblasts, expanded and then cultured under defined conditions to generate a stratified skin tissue representing the essential epidermal layers including the stratum corneum. The approach was extended to various disease models for atopic dermatitis, psoriasis, ichthyosis, and skin cancer. According to the clinical needs, the focus in dermatology lies on drugs for inflammatory skin diseases and skin cancer.


Fig. 1. Effects of UVB on NHK cell survival and proliferation. a) Relationship of UVB dose and NHK cell viability. NHK were exposed to UVB at different doses as indicated in the figure. Cell viability was evaluated by MTT assay using non-UV NHK as a control CTRL, 100 % cell viability); b) UVB and 5-FU exposure inhibited NHK proliferation. NHK at passage 3 were irradiated with UVB at 30 mJ cm -2 and BrdU incorporation was quantified after 24 h as described in Materials and Methods. 5-FU was used as positive controls; * p < 0.05 vs. negative control (CTRL).
Fig. 2. Morphology of keratinocytes and the staining of beta-galactosidase (β-gal). a) Representative photos of NHK were taken at passage 3 (p3) without UVB exposure and b) p3 with UVB exposure at 30 mJ cm -2 ; c) NHK underwent normal culture to passage 5 (p5); d) calculated percent β-gal positive NHK. * p < 0.05 vs. non-UVB p3; #, p < 0.05 vs. p3+UVB. Photos were captured at 100× magnification.
Fig. 3. Flow cytometry analysis of autofluorescence in keratinocytes. The X-axis is autofluorescence detected at 480/530 nm and the Y-axis is the cell count as described in Materials and Methods. a) The autofluorescence of NHK at different cell conditions, i.e., passage 3 (p3), p3 irradiated with UVB 30 mJ cm -2 (p3+UVB), and NHK at passage 5 (p5); b) The bar graph represents the percentage of autofluorescent cells. * p < 0.05 when compared with p3 (non-UVB).
Fig. 5. Hematoxylin-Eosin staining of RHE. a) Epidermis cultured from keratinocytes at passage 3; b) Epidermis cultured from KC passage 3 irradiated with UVB at 30 mJ cm -2 .
Ultraviolet B irradiation-induced keratinocyte senescence and impaired development of 3D epidermal reconstruct

June 2021

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424 Reads

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3 Citations

Acta Pharmaceutica

Ultraviolet B (UVB) induces morphological and functional changes of the skin. This study investigated the effect of UVB on keratinocyte senescence and the development of reconstructed human epidermis (RHE). Primary normal human keratinocytes (NHK) from juvenile foreskin were irradiated with UVB (30 mJ cm−2) and these effects were compared to NHK that underwent senescence in the late passage. UVB enhanced the accumulation of reactive oxygen species (ROS) and halted cell replication as detected by BrdU cell proliferation assay. The senescence phenotype was evaluated by beta-galactosidase (β-gal) staining and qPCR of genes related to senescent regulation, i.e. p16INK4a, cyclin D2, and IFI27. Senescence induced by high dose UVB resulted in morphological changes, enhanced β-gal activity, elevated cellular ROS levels and reduced DNA synthesis. qPCR revealed differential expression of the genes regulated senescence. p16INK4a expression was significantly increased in NHK exposed to UVB whereas enhanced IFI27 expression was observed only in cultural senescence. The levels of cyclin D2 expression were not significantly altered either by UVB or long culturing conditions. UVB significantly induced the aging phenotype in keratinocytes and impaired epidermal development. RHE generated from UVB-irradiated keratinocytes showed a thinner cross-sectional structure and the majority of keratinocytes in the lower epidermis were degenerated. The 3D epidermis model is useful in studying the skin aging process.


Figure 7. Eye irritation potential of polyester particles at the concentration of 0.5% by the EpiOcular test. Mean ± SD, n = 3.
Cont.
Effect of Poly(L-lysine) and Heparin Coatings on the Surface of Polyester-Based Particles on Prednisolone Release and Biocompatibility

May 2021

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177 Reads

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8 Citations

Pharmaceutics

A plethora of micro- and nanoparticle types are currently investigated for advanced ocular treatment due to improved drug retention times, higher bioavailability and better biocompatibility. Yet, comparative studies of both physicochemical and toxicological performance of these novel drug delivery systems are still rare. Herein, poly(L-lactic acid)- and poly(ε-caprolactone)-based micro- and nanoparticles were loaded with prednisolone as a model drug. The physicochemical properties of the particles were varied with respect to their hydrophilicity and size as well as their charge and the effect on prednisolone release was evaluated. The particle biocompatibility was assessed by a two-tier testing strategy, combining the EpiOcularTM eye irritation test and bovine corneal opacity and permeability assay. The biodegradable polyelectrolyte corona on the particles’ surface determined the surface charge and the release rate, enabling prednisolone release for at least 30 days. Thereby, the prednisolone release process was mainly governed by molecular diffusion. Finally, the developed particle formulations were found to be nontoxic in the tested range of concentrations.


Fluorescence label (Rhodamine B, RhoB) properties, intensity and fluorescence lifetime, can be tuned to be both true concentration sensitive when in conjugation with a spin label (3‐carboxy‐proxyl, PCA). Colors mark the read‐out parameters of each label. The resulting dual label (DL) probe provides non‐destructive target detection and quantification as well as characterization of local environment in tissue via FLIM and EPR. Besides tissue applications, a DL‐labeled biomolecule enables in vitro spectroscopic studies of the biomolecular conformation, structure, and dynamics.
Scheme of DL synthesis. PCA (3) and Rhodamine B‐piperazine (5) were covalently linked to Fmoc‐Lys(Boc)‐OH (1) yielding the DL conjugate (6). (2) deprotected Lys(Boc)‐OH, (4) Boc‐Lys‐PCA.
Characterization of DL in phosphate‐buffered saline (PBS) solution and in cryosections from tissue mimetics (agarose gels). A) Normalized absorbance spectra of Rhodamine B (Rho B), DL (6), Rhodamine B‐piperazine (5), and Boc‐Lys‐RhoB‐piperazine for comparison. B) Emission spectra of the compounds shown in (A) at 10 or 12.6 μM (DL). C) Fluorescence decay curves of the compounds shown in (A). D) EPR spectra of 504 μM DL (6) and PCA dissolved in PBS. The correlation time is given. E) Concentration dependence of the fluorescence intensity of RhoB and DL from tissue mimetics using FLIM. F) Concentration dependence of the fluorescence lifetime of RhoB and DL in cryosections from tissue mimetics using FLIM. The errors bars are ± SD (n=3).
Localization and quantification of DL in human skin by EPR and FLIM. A) Sample preparation of skin after DL penetration, EPR measured whole tissue blocks, while for FLIM measurements cryosections were used. B) Brightfield, C) fluorescence intensity, and D) FLIM image with penetration profile. E) Fluorescence lifetime curves from the FLIM cluster image in (D). The concentration calibration is shown in Figure 3 E,F and Figure S18. Comparison of DL concentration in F) whole skin, G) viable epidermis (VE), and H) dermis (DE), determined by EPR and fluorescence lifetime and intensity from FLIM. Error bars are ± SD (n=4). I,J) DL concentrations from (G) and (H) normalized to whole skin.
Sites of DL accumulation. A) Brightfield and B) FLIM images of a hair follicle of the same ROI. C) The viable epidermis and D) the dermis shown by FLIM. E) EPR spectrum of DL in whole skin is a linear combination of pure spectra of DL in a hydrophilic, fast mobility (DLHydro) or less polar, low mobility environment (LME). F) Experimental (solid lines) and simulated (dotted lines) EPR spectra of DL in the viable epidermis (VE) and dermis (DE). All spectra were normalized to the maximum peak intensity. The fraction of DLHydro and the corresponding rotational correlation time (tcorr) in different skin layers are indicated.
A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

May 2021

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387 Reads

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7 Citations

Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label‐mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof‐of‐principle penetration experiments in human skin ex vivo.


Figure 2. Scheme of DL synthesis. PCA (3) and Rhodamine B-piperazine (5) were covalently linked to Fmoc-Lys(Boc)-OH (1) yielding the DL conjugate (6). (2) deprotected Lys(Boc)-OH, (4) Boc-Lys-PCA.
Figure 4. Localization and quantification of DL in human skin by EPR and FLIM. A) Sample preparation of skin after DL penetration, EPR measured whole tissue blocks, while for FLIM measurements cryosections were used. B) Brightfield, C) fluorescence intensity, and D) FLIM image with penetration profile. E) Fluorescence lifetime curves from the FLIM cluster image in (D). The concentration calibration is shown in Figure 3 E,F and Figure S18. Comparison of DL concentration in F) whole skin, G) viable epidermis (VE), and H) dermis (DE), determined by EPR and fluorescence lifetime and intensity from FLIM. Error bars are AE SD (n = 4). I,J) DL concentrations from (G) and (H) normalized to whole skin.
A Dual Fluorescence‐Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM – EPR Spectroscopy

February 2021

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163 Reads

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2 Citations

Angewandte Chemie

A novel multi-label synthetic platform for a functional dual fluorescence–spin label probe enables the non-destructive simultaneous quantification and visualization of molecules in biological tissue. Multiplexed FLIM and EPR spectroscopy avoids analytical inconsistencies between both techniques. Beside tissue applications, molecular spectroscopic studies of biomolecular conformation, structure, dynamics, and microenvironment are feasible. Abstract Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label-mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof-of-principle penetration experiments in human skin ex vivo.


Procedure outline and morphology of NOM and TOM models. (A) Human oral fibroblasts were suspended in a fibrinogen/thrombin solution and poured into a patch with esterified hyaluronic acid fibers (Hyalograft-3D). Fibroblasts replaced the fibrin gel by their own extracellular matrix (day 1–7). Normal oral keratinocytes or tumor cells were seeded on day 7 onto the matrix and grew until day 21 or 56 (2 or 7 weeks with tumor cells). (B) Hematoxylin and eosin and (C) Periodic Acid-Schiff staining. Dark purple structures in both stainings of the lamina propria were hyaluronic acid fibers of the scaffold (black arrows). The inserts show the difference between normal and tumor cell morphology by higher magnification. Representative images from the analysis of up to three batches are presented. Scale bars = 250 and 50 μm in the inserts.
Expression of cytokeratin and laminin-332 in NOM and TOM models. (A) Cytokeratin staining (brown) showed the absence of invasive growth in NOM and c-TOM models. In contrast, nests of cytokeratin positive cells started to infiltrate the lamina propria in h-TOM models after 2 weeks and markedly separated into single cells after 7 weeks. (B) Epithelial thickness in TOM models exceeded those in NOM models. The highest value occurred in h-TOM models after 7 weeks. (C,D) Laminin-332 (green) expression was restricted to a small layer in NOM models and diffusely clustered in TOM models. DAPI stained nuclei and fibers in blue, which could however be distinguished by their size and shape. The inserts show the border between epithelial cells and the matrix, with highest infiltration of the tumor cells in the 7 weeks cultured hyalograft-models, by higher magnification. White arrows highlight fibers and dashed lines indicate the border between epithelium and lamina propria. Representative images from up to three independent cultures are presented. Scale bars = 250 and 50 μm in the inserts. Bar graphs show the mean + SD from the quantitative analysis of up to six regions of interest.
Expression of tenascin c and HIF-1α in NOM and TOM models. (A,B) Tenascin c (red) was less expressed in hyalograft-based models than collagen-based models and further decreased during cultivation. (C,D) HIF-1α (green) showed increased expression in TOM models, with matrix-dependent differences. DAPI stained nuclei and fibers in blue. The inserts show the border between epithelial cells and the matrix for the tenascin C staining and highlights of the HIF-1α staining by higher magnification. White arrows highlight fibers and dashed lines indicate the border between epithelium and lamina propria. Representative images from up to three independent cultures are presented. Scale bar = 250 and 50 μm in the inserts. Bar graphs show the mean + SD from the quantitative analysis of up to six regions of interest of interest.
Expression of vascular endothelial growth factor (VEGF) and proliferation (Ki-67) in NOM and TOM models. (A,B) Highest expression of VEGF (red) was observed in h-TOM models after 7 weeks. (C,D) The number of proliferative cells (Ki-67 positive, green) was increased in TOM models until the end of the cultivation period compared to NOM models. The inserts highlight detected VEGF and Ki-67 in the epithelial layers by higher magnification. Representative images from up to three independent cultures are presented. Scale bars = 250 and 50 μm in the inserts. Bar graphs show the mean + SD from the quantitative analysis of up to six regions of interest.
Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models

December 2020

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118 Reads

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3 Citations

3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main disadvantages of the matrices commonly used for in vitro culture are their limited cultivation time and the low comparability with patient-specific matrix properties. Extended cultivation periods are feasible when primary human cells produce the extracellular matrix in situ. Herein, we adapted the hyalograft-3D approach from reconstructed human skin to normal and tumor oral mucosa models and compared the results to bovine collagen-based models. The hyalograft models showed similar morphology and cell proliferation after 7 weeks compared to collagen-based models after 2 weeks of cultivation. Tumor thickness and VEGF expression increased in hyalograft-based tumor models, whereas expression of laminin-332, tenascin C, and hypoxia-inducible factor 1α was lower than in collagen-based models. Taken together, the in situ produced extracellular matrix better confined tumor invasion in the first part of the cultivation period, with continuous tumor proliferation and increasing invasion later on. This proof-of-concept study showed the successful transfer of the hyalograft approach to tumor oral mucosa models and lays the foundation for the assessment of long-term drug treatment effects. Moreover, the use of an animal-derived extracellular matrix is avoided.


How Qualification of 3D Disease Models Cuts the Gordian Knot in Preclinical Drug Development

September 2020

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31 Reads

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4 Citations

Handbook of Experimental Pharmacology

Preclinical research struggles with its predictive power for drug effects in patients. The clinical success of preclinically approved drug candidates ranges between 3% and 33%. Regardless of the approach, novel disease models and test methods need to prove their relevance and reliability for predicting drug effects in patients, which is usually achieved by method validation. Nevertheless, validating all models appears unrealistic due to the variety of diseases. Thus, novel concepts are needed to increase the quality of preclinical research.


Citations (79)


... SE supplies critical information about cell-cell interactions, the effects of different stimuli on epidermal and dermal cell proliferation, and differentiation. SE was also used in cosmetology testing and drug delivery testing, photoaging, and skin cancer studies (Chouinard et al., 2001;Bom et al., 2021;Graff et al., 2022). Clinically, SE was beneficial in treating three-degree burned patients (Still et al., 2003;Wisser et al., 2004;Hohlfeld et al., 2005). ...

Reference:

Engineering diabetic human skin equivalent for in vitro and in vivo applications
Preclinical Testing of Dendritic Core–Multishell Nanoparticles in Inflammatory Skin Equivalents
  • Citing Article
  • March 2022

Molecular Pharmaceutics

... Principal component analysis (PCA) is often used in chemistry, medicine, and croprelated evaluation [53,54]. In addition, we implement the spatial principal component analysis using ArcMap and statistical methodologies. ...

Correction to: Solvent Effects on Skin Penetration and Spatial Distribution of the Hydrophilic Nitroxide Spin Probe PCA Investigated by EPR

Cell Biochemistry and Biophysics

... However, its direct high-dose administration is frequently linked to adverse inflammatory responses, which can restrict its therapeutic application. This limitation is further exacerbated by the compound's non-targeted action, poor water solubility, and short half-life [24][25][26]. Notably, the utilization of nanodelivery systems can significantly expand the application of PLS. These systems enhance the drug's targeting capabilities, improve its solubility, and prolong its half-life, thereby optimizing therapeutic effectiveness while minimizing adverse effects. ...

Effect of Poly(L-lysine) and Heparin Coatings on the Surface of Polyester-Based Particles on Prednisolone Release and Biocompatibility

Pharmaceutics

... From the in vitro study of skin equivalents, different investigators have reported different results for p16 expression. Some have observed an inverse correlation with the expression of Ki-67, a proliferation marker in skin biopsy, whereas others have reported no change or an increase [76,77]. In addition, nHEKs treated with H 2 O 2 and/or Iris-exosomes did not exhibit any changes in p16 mRNA or protein levels. ...

Ultraviolet B irradiation-induced keratinocyte senescence and impaired development of 3D epidermal reconstruct

Acta Pharmaceutica

... This process is potentially suitable for use as a smart label for the freshness of fish; for example, it can be used with suspected rotten fish without opening the packaged fish container ( Figure 14). Using the combined techniques developed in this process, not only fluorescence but also EPR could be used to characterize the freshness of fish while new applications of dual fluorescence-spin-label probes [37] or sensor arrays [38] are developed for practical use. ...

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

... On the other hand, there is an upward regulation of involucrin, which is expressed by irreversibly differentiated KTs. All these proteins are important in the epidermal barrier function [11]. Moreover, increased expression of certain proteins that are not expressed in healthy skin, such as skin-derived anti-leukoproteinase/elafin, human βdefensin 2 or β-defensin 4 (DEFB4), K6, K16, and K17 is observed [3]. ...

How Qualification of 3D Disease Models Cuts the Gordian Knot in Preclinical Drug Development
  • Citing Article
  • September 2020

Handbook of Experimental Pharmacology

... 50,51 Tumours in vivo adapt to hypoxic conditions associated with rapid growth by modulating hypoxia-inducible factors (HIF) and vascular endothelial growth factor (VEGF). 49,52 This increases expression of EGFR, conferring treatment resistance and cell longevity, as exemplified in a study on HNSCC cell lines by Boeckx et al., 49 in which increased cetuximab sensitivity was noted in a cell line exposed to hypoxia for 72 h. IC 50 values for cetuximab with normoxia, 24 and 72 h of hypoxia were 2.38 ± 0.59 nM, 0.64 ± 0.38 nM, and 0.10 ± 0.05 nM respectively. ...

A multilayered epithelial mucosa model of head neck squamous cell carcinoma for analysis of tumor-microenvironment interactions and drug development
  • Citing Article
  • August 2020

Biomaterials

... The phasor plot is a visualization tool for fluorescence lifetime decay data, which does not assume a specific number of fluorophores prior to analysis (such as in mono-or biexponential fitting). This approach consists of converting the initial data to a phasor plane using their Fourier harmonics [148,149]. A phasor plot can be interpreted through changes in the point cloud position. ...

Faster, sharper, more precise: Automated Cluster-FLIM in preclinical testing directly identifies the intracellular fate of theranostics in live cells and tissue

Theranostics

... Therefore, the aqueous solution applied to the pretreated skin displayed accelerated penetration, which is shown by the continuously increasing slope of the curve ( Figure 10A). However, although pretreatment with solid MNs could create micropores in the skin for diffusion of propranolol hydrochloride, the lipids that reside among the coenocytes may still delay the diffusion of hydrophilic molecules such as propranolol hydrochloride [74,75]. By contrast, the dissolving MNs directly delivered propranolol hydrochloride into the skin, while the needle matrix dissolved rapidly. ...

Solvent Effects on Skin Penetration and Spatial Distribution of the Hydrophilic Nitroxide Spin Probe PCA Investigated by EPR

Cell Biochemistry and Biophysics

... Hormonal changes due to menopause process, which is a natural outcome of aging process in women, can be evaluated using a 3D RHE models based on NHEKs (Mainzer et al, 2018). In addition, a wide range of commercially available 3D reconstructed skin models exist such as ZK1350 (Liebsch et al, 1995), EpiDerm (Lí sková et al, 2020), T-skin (Bataillon et al, 2019), MelanoDerm, (Park et al, 2020), EpiSkin , SkinEthic RHPE 45, and The Phenion FT Skin (Pfuhler et al, 2021) models, which can be used for skin agingerelated studies. ...

Validation of the 3D reconstructed human skin Comet assay, an animal-free alternative for following-up positive results from standard in vitro genotoxicity assays

Mutagenesis