Controlled Release of Doxorubicin from Magnetoliposomes Assisted by Low-Frequency Magnetic Field.

The article presents magnetoliposomes as potential carriers of doxorubicin. The magnetic properties of nanoparticles embedded in liposomes enable the targeting of drug-loaded carriers to cancer cells and subsequent release of their payload using an external alternating magnetic field as a trigger. The cytotoxicity of empty and doxorubicin-loaded magnetoliposomes in the absence and after exposure to magnetic field was evaluated in cancerous and normal breast cells. The characteristic shows the carrier with size distribution <130 nm, slightly negative zeta potential and polydispersity index <0.2. Doxorubicin was encapsulated in magnetoliposomes with an efficiency of 31 % and released in the presence of an alternating magnetic field at 50 %. Magnetoliposomes with drug provided high cytotoxic effect on tumor cells and low cytotoxic effect on normal cells. The research conducted in this article may indicate the potential application of the studied magnetoliposomes in release of drugs under the influence of magnetic field in cancer cells.

Soapwort (Saponaria officinalis L.) Extract vs. Synthetic Surfactants-Effect on Skin-Mimetic Models.

Our skin is continuously exposed to different amphiphilic substances capable of interaction with its lipids and proteins. We describe the effect of a saponin-rich soapwort extract and of four commonly employed synthetic surfactants: sodium lauryl sulfate (SLS), sodium laureth sulfate (SLES), ammonium lauryl sulfate (ALS), cocamidopropyl betaine (CAPB) on different human skin models. Two human skin cell lines were employed: normal keratinocytes (HaCaT) and human melanoma cells (A375). The liposomes consisting of a dipalmitoylphosphatidylcholine/cholesterol mixture in a molar ratio of 7:3, mimicking the cell membrane of keratinocytes and melanoma cells were employed as the second model. Using dynamic light scattering (DLS), the particle size distribution of liposomes was analyzed before and after contact with the tested (bio)surfactants. The results, supplemented by the protein solubilization tests (albumin denaturation test, zein test) and oil emulsification capacity (using olive oil and engine oil), showed that the soapwort extract affects the skin models to a clearly different extent than any of the tested synthetic surfactants. Its protein and lipid solubilizing potential are much smaller than for the three anionic surfactants (SLS, ALS, SLES). In terms of protein solubilization potential, the soapwort extract is comparable to CAPB, which, however, is much harsher to lipids.

Co-delivery of IR-768 and daunorubicin using mPEG-b-PLGA micelles for synergistic enhancement of combination therapy of melanoma.

Malignant melanoma is an emerging problem worldwide due to the high degree of lethalness. Its aggressiveness and the ability to metastasize along with the heterogeneity at the molecular and cellular levels, limit the overall therapeutic efficacy. Despite significant advances in melanoma treatment over the last decade, there is still a need for improved therapeutic modalities. Thus, we demonstrate here a combinatorial approach that targets multiple independent therapeutic pathways, in which polymeric micelles (PMs) were used as efficacious colloidal nanocarriers loaded with both daunorubicin (DRB) as a cytotoxic drug and IR-768 as a photosensitizer. This afforded the dual drug loaded delivery system IR-768 + DRB in PMs. The fabricated mPEG-b-PLGA micelles (hydrodynamic diameters ≈ 25 nm) had a relatively narrow size distribution (PdI > ca. 0.3) with uniform spherical shapes. CLSM study showed that mPEG-b-PLGA micelles were uptaken by mitochondria, which further contributed to excellent singlet oxygen generation capacity for PDT in A375 melanoma cells. Furthermore, the PMs were efficiently internalized by tested cells through endocytosis, resulting in much higher cellular uptake comparing to the free drug. As a result of these properties, IR-768 + DRB in PMs exhibited very potent and synergistically enhanced anticancer activity against A375 cells. Additionally, this combination approach allowed to reduce drug doses and provided low side effects towards normal HaCaT. This study indicates excellent properties of mPEG-b-PLGA micelles resulting in great therapeutic potential possessed by the developed nanoscale drug delivery system for combined chemo-photodynamic therapy of melanoma.

Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors.

The past few years have seen significant developments in the chemistry and potential biological applications of 2D materials. This review focuses on recent advances in the biotechnological and biomedical applications of MXenes, which are 2D carbides, nitrides, and carbonitrides of transition metals. Nanomaterials based on MXenes can be used as therapeutics for anticancer treatment, in photothermal therapy as drug delivery platforms, or as nanodrugs without any additional modification. Furthermore, we discuss the potential use of these materials in biosensing and bioimaging, including magnetic resonance and photoacoustic imaging techniques. Finally, we present the most significant examples of the use of MXenes as efficient agents for environmental and antimicrobial treatments, as well as a brief discussion of their future prospects and challenges.

ZnO nanocrystals derived from organometallic approach: Delineating the role of organic ligand shell on physicochemical properties and nano-specific toxicity.

The surface organic ligands have profound effect on modulation of different physicochemical parameters as well as toxicological profile of semiconductor nanocrystals (NCs). Zinc oxide (ZnO) is one of the most versatile semiconductor material with multifarious potential applications and systematic approach to in-depth understand the interplay between ZnO NCs surface chemistry along with physicochemical properties and their nano-specific toxicity is indispensable for development of ZnO NCs-based devices and biomedical applications. To this end, we have used recently developed the one-pot self-supporting organometallic (OSSOM) approach as a model platform to synthesize a series of ZnO NCs coated with three different alkoxyacetate ligands with varying the ether tail length which simultaneously act as miniPEG prototypes. The ligand coating influence on ZnO NCs physicochemical properties including the inorganic core size, the hydrodynamic diameter, surface charge, photoluminescence (quantum yield and decay time) and ZnO NCs biological activity toward lung cells was thoroughly investigated. The resulting ZnO NCs with average core diameter of 4-5 nm and the hydrodynamic diameter of 8-13 nm exhibit high photoluminescence quantum yield reaching 33% and a dramatic slowing down of charge recombination up to 2.4 µs, which is virtually unaffected by the ligand's character. Nano-specific ZnO NCs-induced cytotoxicity was tested using MTT assay with normal (MRC-5) and cancer (A549) human lung cell lines. Noticeably, no negative effect has been observed up to the NCs concentration of 10 µg/mL and essentially very low negative toxicological impact could be noticed at higher concentrations. In the latter case, the MTT data analysis indicate that there is a subtle interconnection between inorganic core-organic shell dimensions and toxicological profile of ZnO NCs (strikingly, the NCs coated by the carboxylate bearing a medium ether chain length exhibit the lowest toxicity level). The results demonstrate that, when fully optimized, our organometallic self-supporting approach can be a highly promising method to obtain high-quality and bio-stable ligand-coated ZnO NCs.

Magnetic field-assisted selective delivery of doxorubicin to cancer cells using magnetoliposomes as drug nanocarriers.

Magnetoliposomes are promising candidates for the development of selective drug delivery systems in the treatment of cancer. Those nanosystems were tested as carriers of a strong chemotherapeutic agent, doxorubicin, which is used against breast cancer. Herein, the magnetic properties of hydrophobic iron oxide nanoparticles located exclusively in the lipid bilayer were used to release this drug from the magnetoliposomes. The cytotoxic activity of the nanostructures against the normal and cancer cell lines was determined on the basis of cells viability measurement after incubation with different concentrations of these nanomaterials. In the same way, the effectiveness of killing cancer cells in combination with exposure to magnetic field was also evaluated. These experiments confirmed that the nanostructures composed of liposomes and magnetic nanoparticles are not cytotoxic. However, magnetoliposomes loaded with doxorubicin were effective and selective in reducing the viability of human breast tumor cell lines. In this paper, we demonstrated the promising application of the studied magnetoliposomes as carriers of doxorubicin released under the influence of magnetic field in tumor cells.

Ion Chromatographic Fingerprinting of STC-1 Cellular Response for Taste Sensing.

Taste sensing is of great importance in both the pharmaceutical and foodstuff industries, and is currently mainly based on human sensory evaluation. Many approaches based on chemical sensors have been proposed, leading to the development of various electronic tongue systems. However, this approach is limited by the applied recognition methods, which do not consider natural receptors. Biorecognition elements such as taste receptor proteins or whole cells can be involved in the development of taste sensing biosensors usually equipped with various electrochemical transducers. Here, we propose a new approach: intestinal secretin tumor cell line (STC-1) chemosensory cells were applied for taste recognition, and their taste-specific cellular response was decoded from ion chromatographic fingerprints with the use of multivariate data processing by partial least squares discriminant analysis (PLS-DA). This approach could be useful for the development of various non-invasive taste sensing assays, as well as for studying taste transduction mechanisms in vitro.

2D Ti2C (MXene) as a novel highly efficient and selective agent for photothermal therapy.

Photothermal therapy (PTT) has shown significant potential for anti-cancer modality. In this report, according to our best knowledge, we explore for the first time Ti2C-based MXene as a novel, highly efficient and selective agent for photothermal therapy (PTT). Ti2C superficially modified with PEG was obtained from the layered, commercially available Ti2AlC MAX phase in the process of etching aluminum layers using concentrated HF, and characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HREM) as well as X-ray photoelectron spectroscopy for chemical analysis (ESCA-XPS). The PEG-coated Ti2C flakes showed a satisfactory photothermal conversion efficacy (PTCE) and good biocompatibility in wide range of the tested concentrations. Through in vitro studies, the PEG-modified Ti2C demonstrated notable NIR-induced ability to cancerous cells' ablation with minimal impact on non-malignant cells up to the concentration of 37.5 µg mL-1. The applied doses of Ti2C_PEG in our work were even 24 times lower comparing other MXene-based photothermal agents. This work is expected to expand the utility of 2D MXenes to biomedical applications through the development of entirely novel agents for photothermal therapy. This work is expected to expand the utility of 2D MXenes to biomedical applications through the development of entirely novel agents for photothermal therapy.

Recent progress in the engineering of multifunctional colloidal nanoparticles for enhanced photodynamic therapy and bioimaging.

This up-to-date review summarizes the design and current fabrication strategies that have been employed in the area of mono- and multifunctional colloidal nanoparticles - nanocarriers well suited for photodynamic therapy (PDT) and diagnostic purposes. Rationally engineered photosensitizer (PS)-loaded nanoparticles may be achieved via either noncovalent (i.e., self-aggregation, interfacial deposition, interfacial polymerization, or core-shell entrapment along with physical adsorption) or covalent (chemical immobilization or conjugation) processes. These PS loading approaches should provide chemical and physical stability to PS payloads. Their hydrophilic surfaces, capable of appreciable surface interactions with biological systems, can be further modified using functional groups (stealth effect) to achieve prolonged circulation in the body after administration and/or grafted by targeting agents (such as ligands, which bind to specific receptors uniquely expressed on the cell surface) or stimuli (e.g., pH, temperature, and light)-responsive moieties to improve their action and targeting efficiency. These attempts may in principle permit efficacious PDT, combination therapies, molecular diagnosis, and - in the case of nanotheranostics - simultaneous monitoring and treatment. Nanophotosensitizers (nano-PSs) should possess appropriate morphologies, sizes, unimodal distributions and surface processes to be successfully delivered to the place of action after systemic administration and should be accumulated in certain tumors by passive and/or active targeting. Additionally, physically facilitating drug delivery systems emerge as a promising approach to enhancing drug delivery, especially for the non-invasive treatment of deep-seated malignant tissues. Recent advances in nano-PSs are scrutinized, with an emphasis on design principles, via the promising use of colloid chemistry and nanotechnology.

Safe-by-Design Ligand-Coated ZnO Nanocrystals Engineered by an Organometallic Approach: Unique Physicochemical Properties and Low Toxicity toward Lung Cells.

The unique physicochemical properties and biocompatibility of zinc oxide nanocrystals (ZnO NCs) are strongly dependent on the nanocrystal/ligand interface, which is largely determined by synthetic procedures. Stable ZnO NCs coated with a densely packed shell of 2-(2-methoxyethoxy)acetate ligands, which act as miniPEG prototypes, with average core size and hydrodynamic diameter of 4-5 and about 12 nm, respectively, were prepared by an organometallic self-supporting approach, fully characterized, and used as a model system for biological studies. The ZnO NCs from the one-pot, self-supporting organometallic procedure exhibit unique physicochemical properties such as relatively high quantum yield (up to 28 %), ultralong photoluminescence decay (up to 2.1 µs), and EPR silence under standard conditions. The cytotoxicity of the resulting ZnO NCs toward normal (MRC-5) and cancer (A549) human lung cell lines was tested by MTT assay, which demonstrated that these brightly luminescent, quantum-sized ZnO NCs have a low negative impact on mammalian cell lines. These results substantiate that the self-supporting organometallic approach is a highly promising method to obtain high-quality, nontoxic, ligand-coated ZnO NCs with prospective biomedical applications.

Lab-on-a-chip systems for photodynamic therapy investigations.

In recent years photodynamic therapy (PDT) has received widespread attention in cancer treatment due to its smaller surgical trauma, better selectivity towards tumor cells, reduced side effects and possibility of repeatable treatment. Since cancer is the second cause of death worldwide, scientists constantly seek for new potential therapeutic agents including nanotechnology-based photosensitizers used in PDT. The new-designed nanostructures must be carefully studied and well characterized what require analytically useful and powerful tools that enable real progress in nanoscience development. This review describes the current status of PDT investigations using microfluidic Lab-on-a-Chip systems, including recent developments of nanoparticle-based PDT agents, their combinations with different drugs, designs and examples of in vitro applications. This review mainly lays emphasis on biological evaluation of FDA approved photosensitizing agents as well as newly designed nanophotosensitizers. It also highlights the analytical performances of various microfluidic Lab-on-a-chip systems for PDT efficacy analysis on 3D culture and discusses microsystems designs in detail.

3D lung spheroid cultures for evaluation of photodynamic therapy (PDT) procedures in microfluidic Lab-on-a-Chip system.

The purpose of this paper is to present a fully integrated microchip for the evaluation of PDT procedures efficiency on 3D lung spheroid cultures. Human lung carcinoma A549 and non-malignant MRC-5 spheroids were utilized as culture models. Spheroid viability was evaluated 24 h after PDT treatment, in which 5-aminolevulinic acid (ALA) had been used as a precursor of a photosensitizer (protoporphyrin IX - PpIX). Moreover, spheroid viability over a long-term (10-day) culture was also examined. We showed that the proposed PDT treatment was toxic only for cancer spheroids. This could be because of a much-favoured enzymatic conversion of ALA to PpIX in cancer as opposed normal cells. Moreover, we showed that to obtain high effectiveness of ALA-PDT on lung cancer spheroids additional time of spheroid after light exposure was required. It was found that PDT had been effective 5 days after PDT treatment with 3 mM ALA. To the best of our knowledge this has been the first presentation of such research performed on a 3D lung spheroids culture in a microfluidic system.

Studies of anticancer drug cytotoxicity based on long-term HepG2 spheroid culture in a microfluidic system.

Cell-on-a-chip systems have become promising devices to study the effectiveness of new anticancer drugs recently. Several microdevices for liver cancer culture and evaluation of the drug cytotoxicity have been reported. However, there are still no proven reports about high-throughput and simple methods for the evaluation of drug cytotoxicity on liver cancer cells. The paper presents the results of the effects of the anticancer drug (5-fluorouracil, 5-FU) on the HepG2 spheroids as a model of liver cancer. The experiments were based on the long-term 3D spheroid culture in the microfluidic system and monitoring of the effect of 5-FU at two selected concentrations (0.5 mM and 1.0 mM). Our investigations have shown that the initial size of the spheroids has influence on the drug effect. With the increase of the spheroids diameter, the drug resistance (for the two tested 5-FU concentrations) decreases. This phenomenon was observed both through cells metabolism analysis, as well as changes in spheroids sizes. In our research, we have shown that the lower 5-FU (0.5 mM) concentration causes higher decrease in HepG2 spheroids viability. Moreover, due to the microsystem construction, we observe the drug resistance effect (10th day of culture) regardless of the initial size of the created spheroids and the drug concentration.

Soft tissue mesenchymal tumour - a case report with review of literature.

INTRODUCTION: Soft tissue mesenchymal tumours are a common occurrence in surgical practice with particular predilection for the extremities. Approximately 1 in 100 soft tissue tumours are found to be sarcomas. The main concern is to exclude any evidence of malignancy. Both imaging studies and a detailed histological analysis is required to ensure that a diagnosis of a high-grade tumour is not missed. PRESENTATION OF CASE: Here we present a 38-year-old previously fit and well gentleman with a slowly growing lump in the upper aspect of his abdomen over the previous year being completely asymptomatic from it. He underwent ultrasound, computed tomography and magnetic resonance imaging of the lump. He underwent ultrasound guided biopsy with eventual wide local excision of the lump for a complete histological assessment. This was noted to be a soft tissue mesenchymal tumour. DISCUSSION: We highlight the importance of review of the literature and the use of markers that enable histopathologist reach an eventual diagnosis. Mesenchymal tissue during development differentiates into fat, skeletal muscle, peripheral nerves, blood vessels and fibrous tissue. Thereby any of these components may give rise to a tumour. In the majority of cases, the patient is asymptomatic unless there is invasion of nerve sheath or the effects of mass effect. CONCLUSION: Our case is unique due to location of the tumour and its immunohistochemistry findings which required frequent and extensive discussion at our national sarcoma soft tissue meeting. The importance of surgeons working with histopathologists was also highlighted in our case.

Evaluation of nanoencapsulated verteporfin's cytotoxicity using a microfluidic system.

A new-generation of nanoencapsulated photosensitizers could be a good solution to perform effective photodynamic therapy (PDT). In this paper, we present physicochemical characterization and cellular investigation of newly prepared long-sustained release oil-core polyelectrolyte nanocarriers loaded with verteporfin (nano VP) in relation to free VP. For this purpose, a macroscale multiwell plates and multifunctional microfluidic system (for three types of cell cultures: monoculture, coculture and mixed culture) were used. A physical analysis of nano VP showed its high stability, monodispersity with unimodal shape and highly positive charge, what made them good candidates for cancer treatment. Biological properties (cellular internalization and uptake as well as cytotoxicity) of nano and free VP were evaluated using both carcinoma (A549) and normal (MRC-5) human lung cells. It was investigated that verteporfin was accumulated in cancer cells preferentially. Low cytotoxicity of the tested photosensitizer was observed in both macro, and microscale. However, in experiments performed in the microsystem, nano VP allowed the reduction of cytotoxic effect, especially in relation to the normal cells. It could result from the specific environment of cell growth in the microsystem which can quite closely mimic the in vivo conditions. Our results suggest that the presented microsystem could be a very useful microtool for testing of new generation of photosensitizers in various configurations of cell cultures, which are difficult to perform in the macroscale. Moreover, the prepared nano VP could be successfully used for further research i.e. evaluation of PDT procedures.

Microfluidic platform for photodynamic therapy cytotoxicity analysis of nanoencapsulated indocyanine-type photosensitizers.

The application of nanotechnology is important to improve research and development of alternative anticancer therapies. In order to accelerate research related to cancer diagnosis and to improve the effectiveness of cancer treatment, various nanomaterials are being tested. The main objective of this work was basic research focused on examination of the mechanism and effectiveness of the introduction of nanoencapsulated photosensitizers to human carcinoma (A549) and normal cells (MRC-5). Newly encapsulated hydrophobic indocyanine-type photosensitizer (i.e., IR-780) was subjected to in vitro studies to determine its release characteristics on a molecular level. The photosensitizers were delivered to carcinoma and normal cells cultured under model conditions using multiwell plates and with the use of the specially designed hybrid (poly(dimethylsiloxane) (PDMS)/glass) microfluidic system. The specific geometry of our microsystem allows for the examination of intercellular interactions between cells cultured in the microchambers connected with microchannels of precisely defined length. Our microsystem allows investigating various therapeutic procedures (e.g., photodynamic therapy) on monoculture, coculture, and mixed culture, simultaneously, which is very difficult to perform using standard multiwell plates. In addition, we tested the cellular internalization of nanoparticles (differing in size, surface properties) in carcinoma and normal lung cells. We proved that cellular uptake of nanocapsules loaded with cyanine IR-780 in carcinoma cells was more significant than in normal cells. We demonstrated non cytotoxic effect of newly synthesized nanocapsules built with polyelectrolytes (PEs) of opposite surface charges: polyanion-polysodium-4-styrenesulphonate and polycation-poly(diallyldimethyl-ammonium) chloride loaded with cyanine IR-780 on human lung carcinoma and normal cell lines. However, the differences observed in the photocytotoxic effect between two types of tested nanocapsules can result from the type of last PE layer and their different surface charge.

Adhesion of MRC-5 and A549 cells on poly(dimethylsiloxane) surface modified by proteins.

PDMS is a very popular material used for fabrication of Lab-on-a-Chip systems for biological applications. Although PDMS has numerous advantages, it is a highly hydrophobic material, which inhibits adhesion and proliferation of the cells. PDMS surface modifications are used to enrich growth of the cells. However, due to the fact that each cell type has specific adhesion, it is necessary to optimize the parameters of these modifications. In this paper, we present an investigation of normal (MRC-5) and carcinoma (A549) human lung cell adhesion and proliferation on modified PDMS surfaces. We have chosen these cell types because often they are used as models for basic cancer research. To the best of our knowledge, this is the first presentation of this type of investigation. The combination of a gas-phase processing (oxygen plasma or ultraviolet irradiation) and wet chemical methods based on proteins' adsorption was used in our experiments. Different proteins such as poly-l-lysine, fibronectin, laminin, gelatin, and collagen were incubated with the activated PDMS samples. To compare with other works, here, we also examined how ratio of prepolymer to curing agent (5:1, 10:1, and 20:1) influences PDMS hydrophilicity during further modifications. The highest adhesion of the tested cells was observed for the usage of collagen, regardless of PDMS ratio. However, the MRC-5 cell line demonstrated better adhesion than A549 cells. This is probably due to the difference in their morphology and type (normal/cancer).

Role of SAP7-10 and Morphological Regulators (EFG1, CPH1) in Candida albicans' Hypha Formation and Adhesion to Colorectal Carcinoma Caco-2.

Secreted aspartic proteases (Saps) are considered as key virulence factors of Candida albicans. Hopefully our outlook will widen the knowledge of SAP7's role in C. albicans pathogenesis. The goal of our study was to investigate SAP7 expression during C. albicans adhesion to intestinal human cells. Another objective was to study the role of SAP8-10 and transcriptional regulators: EFG1 and CPH1, using the mutants: Δsap, Δefg1, Δcph1 during growth on Caco-2 monolayer. SAP7 expression was analyzed using real time RT-PCR; relative quantification was normalized against ACT1 in cells after growth on Caco-2. Adherence assay of C. albicans to Caco-2 was performed in a 24-well-plate. The results proved that SAP7 can play a role during the initial adaptation of C. albicans to intestinal tract and decreases over time. Up-regulation of SAP7 occured in the absence of SAP8 and SAP10 (genetic alternations dependence). SAP7 can be regulated by the morphogensis' regulators during C. albicans growth on epithelium. Adhesion of the mutants was indistinguishable from SC5314. The lack of neither SAP8-10 nor EFG1/CPH1 influences the adhesive behaviour of C. albicans. Deletion of SAP8-10 resulted in no filamentation defects. The results help better understand the role of SAP7 during adhesion and morphogenesis in C. albicans.

Flow-through sensor array applied to cytotoxicity assessment in cell cultures for drug-testing purposes.

The viability of cells cultured in microsystems for drug screening purposes is usually tested with a variety of colorimetric/fluorescent methods. In this work we propose an alternative way of assessing cell viability-flow-through sensor array that can be connected in series with cell microbioreactors as compatible detection system. It is shown, that the presented device is capable of cytotoxic effect detection and estimation of cell viability after treatment with 1,4-dioxane and 5-fluorouracil, which proves that it can be used for truly non-invasive, fast, reliable, continuous cell culture monitoring in microscale.

A microfluidic system to study the cytotoxic effect of drugs: the combined effect of celecoxib and 5-fluorouracil on normal and cancer cells.

We have investigated the response of normal and cancer cells to exposure a combination of celecoxib (Celbx) and 5-fluorouracil (5-FU) using a lab-on-a-chip microfluidic device. Specifically, we have tested the cytotoxic effect of Celbx on normal mouse embryo cells (Balb/c 3T3) and human lung carcinoma cells (A549). The single drugs or their combinations were adjusted to five different concentrations using a concentration gradient generator (CGG) in a single step. The results suggest that Celbx can enhanced the anticancer activity of 5-FU by stronger inhibition of cancer cell growth. We also show that the A549 cancer cells are more sensitive to Celbx than the Balb/c 3T3 normal cells. The results obtained with the microfluidic system were compared to those obtained with a macroscale in vitro cell culture method. In our opinion, the microfluidic system represents a unique approach for an evaluation of cellular response to multidrug exposure that also is more simple than respective microwell plate assays. Figureᅟ