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Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested. Furthermore, we performed a microarray analysis on ADMSCs treated with individual statins (12 µM) and compared the importance of the effects of statins on gene expression between stem cells and pancreatic cancer cells. Concentrations of statins that significantly affected cancer cells viability (< 40 µM) did not affect stem cells viability after 24 h. Moreover, statins that didn´t affect viability of cancer cells grown in a monolayer, induce the disintegration of cancer cell spheroids. The effect of statins on gene expression was significantly less pronounced in stem cells compared to pancreatic cancer cells. In conclusion, the low efficacy of statins on non-tumor and stem cells at concentrations sufficient for cancer cells growth inhibition, support their applicability in chemoadjuvant tumor therapy.
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Supervivencia Celular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Células Madre Mesenquimatosas , Neoplasias Pancreáticas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Línea Celular Tumoral , Esferoides Celulares/efectos de los fármacos , Células HEK293RESUMEN
Cytochalasans are fungal metabolites that are known to inhibit actin polymerization. Despite their remarkable bioactivity, there are few studies on the structure-activity relationship (SAR) of the cytochalasan scaffold. The full potential of structural modifications remains largely unexplored. The substituent at position 10 of the cytochalasan scaffold is derived from an amino acid incorporated into the cytochalasan core, thus limiting the structural variability at this position in natural products. Additionally, modifications at this position have only been achieved through semisynthetic or mutasynthetic approaches using modified amino acids. This paper introduces a modular approach for late-stage modifications at position 10 of the cytochalasan scaffold. Iron-mediated cross-coupling reactions with corresponding Grignard reagents were used to introduce aryl or benzyl groups in position 10, resulting in the synthesis of six new cytochalasan analogues bearing non-natural aromatic residues. This methodology enables further exploration of modifications at this position and SAR studies among cytochalasan analogues.
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Citocalasinas , Citocalasinas/química , Citocalasinas/farmacología , Citocalasinas/síntesis química , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Improving the anticancer efficacy of chemotherapeutic drugs and photosensitizers requires innovative multifunctional nanoplatforms. This study introduces a chemo- and phototherapeutic drug delivery system (DDS) based on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), both PEGylated and non-PEGylated, with a mean size of 200 ± 75 nm. Colchicine (Colch) and purpurin18 (P18) were co-encapsulated into these NPs, and their in vitro drug release profiles were investigated. The anticancer potential of these systems was evaluated across various cell lines (i.e., CaCo-2, PC-3, MCF-7, and MRC-5 cells), demonstrating enhanced NP uptake by cancer cells compared to free drugs. Co-administration of Colch and P18 in 2D and 3D cell line models exhibited a synergistic effect, harnessing both chemotherapeutic and photodynamic effects, leading to higher cancer cell elimination efficacy. This newly developed multifunctional DDS presents a promising platform for combined chemo- and photodynamic therapy in cancer treatment.
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Colchicina , Portadores de Fármacos , Liberación de Fármacos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Humanos , Colchicina/administración & dosificación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Portadores de Fármacos/química , Línea Celular Tumoral , Esferoides Celulares/efectos de los fármacos , Nanopartículas/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Neoplasias/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Here, we present surface analysis and biocompatibility evaluation of novel composite material based on graphene oxide traded as Hastalex. First, the surface morphology and elemental analysis of the pristine material were examined by atomic force and scanning electron microscopies, and by energy-dispersive and X-ray photoelectron spectroscopies, respectively. The Hastalex surface was then modified by plasma (3 and 8 W with exposure times up to 240 s), the impact of which on the material surface wettability and morphology was further evaluated. In addition, the material aging was studied at room and elevated temperatures. Significant changes in surface roughness, morphology, and area were detected at the nanometer scale after plasma exposure. An increase in oxygen content due to the plasma exposure was observed both for 3 and 8 W. The plasma treatment had an outstanding effect on the cytocompatibility of Hastalex foil treated at both input powers of 3 and 8 W. The cell number of human MRC-5 fibroblasts on Hastalex foils exposed to plasma increased significantly compared to pristine Hastalex and even to tissue culture polystyrene. The plasma exposure also affected the fibroblasts' cell growth and shape.
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We focused on polydimethylsiloxane (PDMS) as a substrate for replication, micropatterning, and construction of biologically active surfaces. The novelty of this study is based on the combination of the argon plasma exposure of a micropatterned PDMS scaffold, where the plasma served as a strong tool for subsequent grafting of collagen coatings and their application as cell growth scaffolds, where the standard was significantly exceeded. As part of the scaffold design, templates with a patterned microstructure of different dimensions (50 × 50, 50 × 20, and 30 × 30 µm2) were created by photolithography followed by pattern replication on a PDMS polymer substrate. Subsequently, the prepared microstructured PDMS replicas were coated with a type I collagen layer. The sample preparation was followed by the characterization of material surface properties using various analytical techniques, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). To evaluate the biocompatibility of the produced samples, we conducted studies on the interactions between selected polymer replicas and micro- and nanostructures and mammalian cells. Specifically, we utilized mouse myoblasts (C2C12), and our results demonstrate that we achieved excellent cell alignment in conjunction with the development of a cytocompatible surface. Consequently, the outcomes of this research contribute to an enhanced comprehension of surface properties and interactions between structured polymers and mammalian cells. The use of periodic microstructures has the potential to advance the creation of novel materials and scaffolds in tissue engineering. These materials exhibit exceptional biocompatibility and possess the capacity to promote cell adhesion and growth.
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Colágeno , Ingeniería de Tejidos , Ratones , Animales , Colágeno/química , Adhesión Celular , Propiedades de Superficie , Mioblastos , Dimetilpolisiloxanos/química , MamíferosRESUMEN
Many bio-applicable materials, medical devices, and prosthetics combine both polymer and metal components to benefit from their complementary properties. This goal is normally achieved by their mechanical bonding or casting only. Here, we report an alternative easy method for the chemical grafting of a polymer on the surfaces of a metal or metal alloys using alkoxy amine salt as a coupling agent. The surface morphology of the created composites was studied by various microscopy methods, and their surface area and porosity were determined by adsorption/desorption nitrogen isotherms. The surface chemical composition was also examined by various spectroscopy techniques and electrokinetic analysis. The distribution of elements on the surface was determined, and the successful bonding of the metal/alloys on one side with the polymer on the other by alkoxy amine was confirmed. The composites show significantly increased hydrophilicity, reliable chemical stability of the bonding, even interaction with solvent for thirty cycles, and up to 95% less bacterial adhesion for the modified samples in comparison with pristine samples, i.e., characteristics that are promising for their application in the biomedical field, such as for implants, prosthetics, etc. All this uses universal, two-step procedures with minimal use of energy and the possibility of production on a mass scale.
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Cytochalasans are known as inhibitors of actin polymerization and for their cytotoxic and migrastatic activity. In this study, we synthesized a series of cytochalasin derivatives that lack a macrocyclic moiety, a structural element traditionally considered essential for their biological activity. We focused on substituting the macrocycle with simple aryl-containing sidechains, and we have also synthesized compounds with different substitution patterns on the cytochalasin core. The cytochalasin analogues were screened for their migrastatic and cytotoxic activity. Compound 24 which shares the substitution pattern with natural cytochalasins B and D exhibited not only significant in vitro migrastatic activity towards BLM cells but also demonstrated inhibition of actin polymerization, with no cytotoxic effect observed at 50 µM concentration. Our results demonstrate that even compounds lacking the macrocyclic moiety can exhibit biological activities, albeit less pronounced than those of natural cytochalasins. However, our findings emphasize the pivotal role of substituting the core structure in switching between migrastatic activity and cytotoxicity. These findings hold significant promise for further development of easily accessible cytochalasan analogues as novel migrastatic agents.
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The design of functional micro or nanostructured surfaces is undergoing extensive research for their intriguing multifunctional properties and for large variety of potential applications in biomedical field (tissue engineering or cell adhesion), electronics, optics or microfluidics. Such nanosized topographies can be easily fabricated by various lithography techniques and can be also further reinforced by synergic effect by combining aforementioned structures along materials with already outstanding antibacterial properties. In this work we fabricated novel micro/nanostructured substrates using soft lithography replication method and subsequent thermal nanoimprint lithography method, creating nanostructured films based on poly (l-lactic acid) (PLLA) fortified by thin silver films deposited by PVD. Main nanoscale patterns were fabricated by replicating surface patterns of optical discs (CDs and DVDs), which proved to be easy, fast and inexpensive method for creating relatively large area patterned surfaces. Their antimicrobial activity was examined in vitro against the bacteria Escherichia coli and Staphylococcus epidermidis strains. The results demonstrated that nanopatterned films actually improved the conditions for bacterial growth compared to pristine PLLA films, the novelty is based on formation of Ag nanoparticles on the surface/and in bulk, while silver nanoparticle enhanced and nanopatterned films exhibited excellent antibacterial activity against both bacterial strains, with circa 80 % efficacy in 4 h and complete bactericidal effect in span of 24 h.
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Photodynamic therapy is an effective method for the treatment of several types of cancerous and noncancerous diseases. The key to the success of this treatment method is effective drug delivery to the site of action, for instance, a tumor. This ensures not only the high effectiveness of the therapy but also the suppression of side effects. But how to achieve effective targeted delivery? Lately, much attention has been paid to systems based on the so-called Trojan horse model, which is gaining increasing popularity. The principle of this model is that the effective drug is hidden in the internal structure of a nanoparticle, liposome, or nanoemulsion and is released only at the site of action. In this review article, we focus on drugs from the group of mitotic poisons, taxanes, and their use with photosensitizers in combined therapy. Here, we discuss the possibilities of how to improve the paclitaxel and docetaxel bioavailability, as well as their specific targeting for use in combined photo- and chemotherapy. Moreover, we also present the state of the art multifunctional drugs based on cabazitaxel which, owing to a suitable combination with photosensitizers, can be used besides photodynamic therapy and also in photoacoustic imaging or sonodynamic therapy.
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Sistemas de Liberación de Medicamentos , Taxoides/farmacología , Taxoides/uso terapéutico , Paclitaxel/farmacologíaRESUMEN
Here, we report poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAm-co-AAc) microgel-loaded polycaprolactone (PCL) nanofibers as temperature-, pH- and electro-responsive materials. First, the PNIPAm-co-AAc microgels were prepared by precipitation polymerization and then electrospun with PCL. The morphology of the prepared materials, analysed by scanning electron microscopy, showed a narrow nanofiber distribution in the range of 500-800 nm, depending on microgel content. Refractometry measurements, performed at pH4 and 6.5, as well as in distilled water, indicated the thermo- and pH-responsive behaviour of the nanofibers between 31 and 34 °C. After being thoroughly characterized, the prepared nanofibers were loaded with crystal violet (CV) or gentamicin as model drugs. The application of a pulsed voltage led to a pronounced increase in drug release kinetics, which was also dependent on microgel content. In addition, long-term temperature- and pH-responsive release was demonstrated. Next, the prepared materials displayed switchable antibacterial activity against S. aureus and E. coli. Finally, cell compatibility tests showed that NIH 3T3 fibroblasts spread evenly over the nanofiber surface, confirming that the nanofibers serve as a favourable support for cell growth. Overall, the prepared nanofibers offer switchable drug release and appear to have considerable biomedical potential, particularly in wound healing.
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Microgeles , Nanofibras , Nanofibras/química , Liberación de Fármacos , Staphylococcus aureus , Escherichia coliRESUMEN
Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance significantly decreases its anticancer effectivity. The main reason for the resistance development is the paclitaxel-induced phenomenon of cytoprotective autophagy occurring by different mechanisms of action in dependence on a cell type and possibly even leading to metastases. Paclitaxel also induces autophagy in cancer stem cells, which greatly contributes to tumor resistance development. Paclitaxel anticancer effectivity can be predicted by the presence of several autophagy-related molecular markers, such as tumor necrosis factor superfamily member 13 in triple-negative breast cancer or cystine/glutamate transporter encoded by the SLC7A11 gene in ovarian cancer. Nevertheless, the undesired effects of paclitaxel-induced autophagy can be eliminated by paclitaxel co-administration with autophagy inhibitors, such as chloroquine. Interestingly, in certain cases, it is worthy of potentiating autophagy by paclitaxel combination with autophagy inducers, for instance, apatinib. A modern strategy in anticancer research is also to encapsulate chemotherapeutics into nanoparticle carriers or develop their novel derivatives with improved anticancer properties. Hence, in this review article, we summarize not only the current knowledge of paclitaxel-induced autophagy and its role in cancer resistance but mainly the possible drug combinations based on paclitaxel and their administration in nanoparticle-based formulations as well as paclitaxel analogs with autophagy-modulating properties.
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Antineoplásicos Fitogénicos , Neoplasias Ováricas , Femenino , Humanos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis , Autofagia , Línea Celular Tumoral , Resistencia a AntineoplásicosRESUMEN
New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18-65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA).
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Here, we aimed at the preparation of an antibacterial surface on a flexible polydimethylsiloxane substrate. The polydimethylsiloxane surface was sputtered with silver, deposited with carbon, heat treated and exposed to excimer laser, and the combinations of these steps were studied. Our main aim was to find the combination of techniques applicable both against Gram-positive and Gram-negative bacteria. The surface morphology of the structures was determined by atomic force microscopy and scanning electron microscopy. Changes in surface chemistry were conducted by application of X-ray photoelectron spectroscopy and energy dispersive spectroscopy. The changes in surface wettability were characterized by surface free energy determination. The heat treatment was also applied to selected samples to study the influence of the process on layer stability and formation of PDMS-Ag or PDMS-C-Ag composite layer. Plasmon resonance effect was determined for as-sputtered and heat-treated Ag on polydimethylsiloxane. The heating of such structures may induce formation of a pattern with a surface plasmon resonance effect, which may also significantly affect the antibacterial activity. We have implemented sputtering of the carbon base layer in combination with excimer laser exposure of PDMS/C/Ag to modify its properties. We have confirmed that deposition of primary carbon layer on PDMS, followed by sputtering of silver combined with subsequent heat treatment and activation of such surface with excimer laser, led to the formation of a surface with strong antibacterial properties against two bacterial strains of S. epidermidis and E. coli.
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Here, we report on the nanopatterning of different aromatic polymer substrates achieved by KrF excimer laser treatment. The conditions for the construction of the laser-induced periodic surface structures, the so-called LIPSS pattern, were established by optimized laser fluence and a number of pulses. The polymer substrates were polyethylene naphthalate (PEN), polyethersulfone (PES), and polystyrene (PS), which were chosen since they are thermally, chemically, and mechanically resistant polymers with high absorption coefficients at the excimer laser wavelength. The surface morphology of the treated substrates was investigated by atomic force microscopy and scanning electron microscopy, and the roughness and effective surface area on the modified samples were determined. Elemental concentration was characterized by energy-dispersive (EDX) analysis, surface chemistry was determined with X-ray photoelectron spectroscopy (XPS). The samples with the formation of LIPSS induced by 10 mJ·cm-2 with 1000, 3000, and 6000 pulses were used for subsequent in vitro cytocompatibility tests using human cells from osteosarcoma (U-2 OS). The LIPSS pattern and its ability of significant cell guidance were confirmed for some of the studied samples. Cell morphology, adhesion, and proliferation were evaluated. The results strongly contribute to the development of novel applications using nanopatterned polymers, e.g., in tissue engineering, cell analysis or in combination with metallization for sensor construction.
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Nanoestructuras , Animales , Comunicación Celular , Humanos , Rayos Láser , Mamíferos , Nanoestructuras/química , Polímeros/química , Propiedades de SuperficieRESUMEN
Nanofibers are an attractive option in drug release, especially as antibacterial materials. However, there is no universal antibacterial material and little attention has been devoted to bacteria-nanofiber attachment. Poly(N-isopropylacrylamide-co-acrylamide) is particularly interesting due to its dual thermo- and pH-responsive nature. Here, we prepared stimuli-responsive antibacterial nanofibers by the blend electrospinning of polycaprolactone (PCL), various concentrations of PNIPAm-co-AAm and ciprofloxacin (CIP). The lower critical solution temperature (LCST) of PNIPAm-co-AAm was determined by refractometry in distilled water and buffer solutions at pH 4 and 7.4. Based on the results obtained, we performed release tests, which indicated that the amount of released CIP and its release kinetics were dependent on nanofiber composition. Moreover, the nanofibers showed enhanced release at temperatures below LCST and, in turn, this led to enhanced antibacterial activity, as demonstrated by disk diffusion tests on Staphylococcus epidermidis and Escherichia coli. In addition, both bacterial strains demonstrated much lower attachment to CIP-loaded PCL/PNIPAm-co-AAm compared with CIP-loaded PCL nanofibers. Furthermore, cytocompatibility tests, performed using primary human dermal fibroblasts, produced similar good cell spreading regardless of PNIPAm-co-AAm concentration. Collectively, our results show that the proposed nanofibers have considerable potential as materials, which promote wound healing and significantly decrease the probability of bacterial infection.
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Nanofibras , Acrilamida , Resinas Acrílicas , Antibacterianos/farmacología , Ciprofloxacina/farmacología , Escherichia coli , Humanos , Concentración de Iones de Hidrógeno , Nanofibras/química , PoliésteresRESUMEN
A polydimethylsiloxane (PDMS) composite with multi-walled carbon nanotubes was successfully prepared. Composite foils were treated with both plasma and excimer laser, and changes in their physicochemical properties were determined in detail. Mainly changes in surface chemistry, wettability, and morphology were determined. The plasma treatment of PDMS complemented with subsequent heating led to the formation of a unique wrinkle-like pattern. The impact of different laser treatment conditions on the composite surface was determined. The morphology was determined by AFM and LCM techniques, while chemical changes and chemical surface mapping were studied with the EDS/EDX method. Selected activated polymer composites were used for the evaluation of antibacterial activity using Gram-positive (Staphylococcus epidermidis) and Gram-negative (Escherichia coli) bacteria. The antibacterial effect was achieved against S. epidermidis on pristine PDMS treated with 500 mJ of laser energy and PDMS-C nanocomposite treated with a lower laser fluence of 250 mJ. Silver deposition of PDMS foil increases significantly its antibacterial properties against E. coli, which is further enhanced by the carbon predeposition or high-energy laser treatment.
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Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.
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Anticuerpos Monoclonales/química , Neoplasias Colorrectales/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Inmunoconjugados/farmacología , Nanopartículas/administración & dosificación , Oxaliplatino/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Antígeno AC133/inmunología , Antineoplásicos/química , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Nanopartículas/químicaRESUMEN
The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.
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Anestésicos Disociativos/efectos adversos , Drogas Ilícitas/efectos adversos , Piperidinas/efectos adversos , Células Cultivadas , Humanos , Psicotrópicos/efectos adversos , Difracción de Rayos X/métodosRESUMEN
Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice.
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Autofagia , Glicósidos Cardíacos/farmacología , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Biomarcadores/metabolismo , Humanos , Modelos Biológicos , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Bacterial environmental colonization and subsequent biofilm formation on surfaces represents a significant and alarming problem in various fields, ranging from contamination of medical devices up to safe food packaging. Therefore, the development of surfaces resistant to bacterial colonization is a challenging and actively solved task. In this field, the current promising direction is the design and creation of nanostructured smart surfaces with on-demand activated amicrobial protection. Various surface activation methods have been described recently. In this review article, we focused on the "physical" activation of nanostructured surfaces. In the first part of the review, we briefly describe the basic principles and common approaches of external stimulus application and surface activation, including the temperature-, light-, electric- or magnetic-field-based surface triggering, as well as mechanically induced surface antimicrobial protection. In the latter part, the recent achievements in the field of smart antimicrobial surfaces with physical activation are discussed, with special attention on multiresponsive or multifunctional physically activated coatings. In particular, we mainly discussed the multistimuli surface triggering, which ensures a better degree of surface properties control, as well as simultaneous utilization of several strategies for surface protection, based on a principally different mechanism of antimicrobial action. We also mentioned several recent trends, including the development of the to-detect and to-kill hybrid approach, which ensures the surface activation in a right place at a right time.