Application of carbon-based quantum dots in photodynamic therapy. - In: Carbon, ISSN 0008-6223, Bd. 203 (2023), S. 273-310
Photodynamic Therapy (PDT) is a non-invasive therapeutic modality that can treat a wide variety of cancer types by means of photosensitizer drug, light, and oxygen. Due to enhanced specificity and fewer side effects, PDT can be an alternative approach for cancer treatments. However, conventional photosensitizers (PSs) exhibit low selectivity, hydrophobicity, and limited photophysical properties. Nanotechnology emerges as a potential solution to these issues and improves PDT efficiency. Nanomaterials such as Carbon Quantum Dots (CQDs) and Graphene Quantum Dots (GrQDs) have been widely applied on PDT research recently, regarding their excellent photoluminescence properties, biocompatibility, as well as their hydrophilicity. The present review article summarizes the main features of PDT and carbon-based quantum dots with an emphasis on used PSs and methods for synthesis of carbon dots. Additionally, the most recent applications of CQDs and GrQDs in PDT have been extensively discussed. The main conclusion that arises is that carbon-based quantum dots seem to be a powerful tool in cancer diagnosis and treatment.
Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer. - In: Nanoscale advances, ISSN 2516-0230, Bd. 4 (2022), 23, S. 5077-5088
The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs - doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs’ toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.
Induction of embryogenic development in haploid microspore stem cells in droplet-based microfluidics. - In: Lab on a chip, ISSN 1473-0189, Bd. 22 (2022), 22, S. 4292-4305
This work presents the application of droplet-based microfluidics for the cultivation of microspores from Brassica napus using the doubled haploid technology. Under stress conditions (e.g. heat shock) or by chemical induction a certain fraction of the microspores can be reprogrammed and androgenesis can be induced. This process is an important approach for plant breeding because desired plant properties can be anchored in the germline on a genetic level. However, the reprogramming rate of the microspores is generally very low, increasing it by specific stimulation is, therefore, both a necessary and challenging task. In order to accelerate the optimisation and development process, the application of droplet-based microfluidics can be a promising tool. Here, we used a tube-based microfluidic system for the generation and cultivation of microspores inside nL-droplets. Different factors like cell density, tube material and heat shock conditions were investigated to improve the yield of vital plant organoids. Evaluation and analysis of the stimuli response were done on an image base aided by an artificial intelligence cell detection algorithm. Droplet-based microfluidics allowed us to apply large concentration programs in small test volumes and to screen the best conditions for reprogramming cells by the histone deacetylase inhibitor trichostatin A and for enhancing the yield of vital microspores in droplets. An enhanced reprogramming rate was found under the heat shock conditions at 32 ˚C for about 3 to 6 days. In addition, the comparative experiment with MTP showed that droplet cultivation with lower cell density (<10 cells per droplet) or adding media after 3 or 6 days significantly positively affects the microspore growth and embryo rate inside 120 nL droplets. Finally, the developed embryos could be removed from the droplets and further grown into mature plants. Overall, we demonstrated that the droplet-based tube system is suitable for implementation in an automated, miniaturized system to achieve the induction of embryogenic development in haploid microspore stem cells of Brassica napus.
In vitro-Amplifikation humaner hämatopoetischer Stammzellen im 3D-System. - In: Biospektrum, ISSN 1868-6249, Bd. 28 (2022), 5, S. 489-492
A promising strategy to increase the numbers of hematopoietic stem cells (HSCs) for clinical applications, like stem cell transplantation, is offered by advanced in vitro culture systems. We developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) mimicking the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized culture medium allow the amplification of high numbers of undifferentiated HSCs by activating specific molecular signaling pathways.
Bidentate Rh(I)-phosphine complexes for the C-H activation of alkanes: computational modelling and mechanistic insight. - In: ChemCatChem, ISSN 1867-3899, Bd. 14 (2022), 18, e202200854, S. 1-9
The C-H activation and subsequent carbonylation mediated by metal complexes, i. e., Rh(I) complexes, has drawn considerable attention in the past. To extend the mechanistic insight from Rh complexes featuring monodentate ligands like P(Me)3 towards more active bisphosphines (PLP), a computationally derived fully conclusive mechanistic picture of the Rh(I)-catalyzed C-H activation and carbonylation is presented here. Depending on the nature of the bisphosphine ligand, the highest lying transition state (TS) is associated either to the initial C-H activation in [Rh(PLP)(CO)(Cl)] or to the rearrangement of the chloride in [Rh(PLP)(H)(R)(Cl)]. The chloride rearrangement was found to play a key role in the subsequent carbonylation. A set of 20 complexes of different architectures was studied, in order to fine tune the C-H activation in a knowledge-driven approach. The computational analysis suggests that a flexible ligand architecture with aromatic rings can potentially increase the performance of Rh-based catalysts for the C-H activation.
A droplet-based microfluidic platform enables high-throughput combinatorial optimization of cyanobacterial cultivation. - In: Scientific reports, ISSN 2045-2322, Bd. 12 (2022), 15536, insges. 12 S.
Cyanobacteria are fast-growing, genetically accessible, photoautotrophs. Therefore, they have attracted interest as sustainable production platforms. However, the lack of techniques to systematically optimize cultivation parameters in a high-throughput manner is holding back progress towards industrialization. To overcome this bottleneck, here we introduce a droplet-based microfluidic platform capable of one- (1D) and two-dimension (2D) screening of key parameters in cyanobacterial cultivation. We successfully grew three different unicellular, biotechnologically relevant, cyanobacteria: Synechocystis sp. PCC 6803, Synechococcus elongatus UTEX 2973 and Synechococcus sp. UTEX 3154. This was followed by a highly-resolved 1D screening of nitrate, phosphate, carbonate, and salt concentrations. The 1D screening results suggested that nitrate and/or phosphate may be limiting nutrients in standard cultivation media. Finally, we use 2D screening to determine the optimal N:P ratio of BG-11. Application of the improved medium composition in a high-density cultivation setup led to an increase in biomass yield of up to 15.7%. This study demonstrates that droplet-based microfluidics can decrease the volume required for cyanobacterial cultivation and screening up to a thousand times while significantly increasing the multiplexing capacity. Going forward, microfluidics have the potential to play a significant role in the industrial exploitation of cyanobacteria.
Contactless optical and impedimetric sensing for droplet-based dose-response investigations of microorganisms. - In: Sensors and actuators, ISSN 0925-4005, Bd. 372 (2022), 132688
The principle of droplet-based microfluidics was used for the characterization of dose/response functions of the soil bacteria Rhodococcus sp. and Chromobacterium vaccinii using a combination of optical and electrical sensors for the detection of bacterial growth and metabolic activity. For electrical characterization, a micro flow-through impedance module was developed which assessed the response of bacterial populations inside 500 nL fluid segments without direct galvanic contact between the electrodes and the electrolyte. It was found that the impedance sensor can detect an increase in cell density and is particularly suited for monitoring the metabolic response due to changes in the cultivation medium inside the separated fluid segments. Due to this sensitivity, the sensor is useful for investigating growing bacteria or cell cultures in small fluid compartments and obtaining highly resolved dose-response functions by microfluid segment sequences. The impedimetric data agree well with the optical data concerning the characteristic response of bacteria populations in the different concentration regions of heavy metal ions. However, the sensor supplies valuable complementary data on metabolic activity in case of low or negligible cell division rates.
Structure elucidation and toxicological evaluation of cyclic Polyethersulfone oligomers present in extracts of membrane filters. - In: Polymer engineering & science, ISSN 1548-2634, Bd. 62 (2022), 9, S. 2817-2825
Polyethersulfone (PES) is a widely used polymer in consumer and technical products. An important application is PES membranes used in the biopharmaceutical industry for sterilizing-grade filtration and for filtration of food and beverages. For both uses, detailed information about migrating compounds that can be extracted from the polymeric material into a liquid must be gathered. In the pharmaceutical industry, comprehensive extractables studies are required for contact materials, and the data is used in the qualification of the process equipment. PES is generated via polycondensation, which forms cyclic oligomers as a by-product of the reaction. However, no structural information is available for these cyclic oligomers so far. In this publication, we present the analytical determination of PES cyclic oligomers. Their presence in extracts of PES membrane filters is confirmed. The structure of the PES cyclic trimer is elucidated by X-ray and NMR investigation, obtained as crystals from the sublimation of the PES raw material. A strategy is shown to assess the toxicity of such cyclic oligomers and to derive a permitted daily exposure (PDE). The data will reduce the levels of unknowns in extractables and leachables screenings and supports the risk assessment of PES sterile filters.
Three soil bacterial communities from an archaeological excavation site of an ancient coal mine near Bennstedt (Germany) characterized by 16S r-RNA sequencing. - In: Environments, ISSN 2076-3298, Bd. 9 (2022), 9, 115, S. 1-19
This metagenomics investigation of three closely adjacent sampling sites from an archaeological excavation of a pre-industrial coal mining exploration shaft provides detailed information on the composition of the local soil bacterial communities. The observed significant differences between the samples, reflected in the 16S r-RNA analyses, were consistent with the archaeologically observed situation distinguishing the coal seam, the rapidly deposited bright sediment inside an exploration shaft, and the topsoil sediment. In general, the soils were characterized by a dominance of Proteobacteria, Actinobacteria, Acidobacteria, and Archaea, whereas the coal seam was characterized by the highest proportion of Proteobacteria; the topsoil was characterized by very high proportions of Archaea - in particular, Nitrosotaleaceae - and Acidobacteria, mainly of Subgroup 2. Interestingly, the samples of the fast-deposited bright sediment showed a rank function of OTU abundances with disproportional values in the lower abundance range. This could be interpreted as a reflection of the rapid redeposition of soil material during the refilling of the exploration shaft in the composition of the soil bacterial community. This interpretation is supported by the observation of a comparatively high proportion of reads relating to bacteria known to be alkaliphilic in this soil material. In summary, these investigations confirm that metagenomic analyses of soil material from archaeological excavations can provide valuable information about the local soil bacterial communities and the historical human impacts on them.
Prestine C60 fullerene as a novel agent in sonodynamic treatment of cancer cells. - In: FEBS Open Bio, ISSN 2211-5463, Bd. 12 (2022), S. 74