Cancer disease has a complicated pathophysiology and is one of the major causes of death and morbidity. Classical cancer therapies include chemotherapy, radiation therapy, and immunotherapy. A typical treatment is chemotherapy, which delivers cytotoxic medications to patients to suppress the uncontrolled growth of cancerous cells. Conventional oral medication has a number of drawbacks, including a lack of selectivity, cytotoxicity, and multi-drug resistance, all of which offer significant obstacles to effective cancer treatment. Multidrug resistance (MDR) remains a major challenge for effective cancer chemotherapeutic interventions. The advent of nanotechnology approach has developed the field of tumor diagnosis and treatment. Cancer nanotechnology enables direct access to tumor cells, resulting in enhanced drug localization and cellular uptake. Since the early 1990's, several solid lipid nanoparticle (SLN) or SLN-based systems for the delivery of cytotoxic drugs have been manufactured and tested with success. High shear homogenization, microemulsion-based SLN, Supercritical fluid technology, spray drying, and solvent emulsification/evaporation methods can all be used to successfully formulate SLN.There is great potential to enhance cancer chemotherapy by incorporating it into a solid lipid nanoparticle (SLN) drug delivery system. Improving tumor diffusivity, improvement of body distribution, and inhibiting MDR are the main attributes. This type of review article discusses advantages and disadvantages of SLNs, their production techniques, and their potential usage in the treatment of various cancers.
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.
- MeSH
- antigen AC133 imunologie MeSH
- antitumorózní látky chemie MeSH
- imunokonjugáty farmakologie MeSH
- kolorektální nádory farmakoterapie imunologie patologie MeSH
- kopolymer kyseliny glykolové a mléčné chemie MeSH
- lidé MeSH
- monoklonální protilátky chemie MeSH
- nanočástice aplikace a dávkování chemie MeSH
- nosiče léků chemie MeSH
- oxaliplatin chemie MeSH
- systémy cílené aplikace léků * MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Silicon dioxide, in the form of nanoparticles, possesses unique physicochemical properties (size, shape, and a large surface to volume ratio). Therefore, it is one of the most promising materials used in biomedicine. In this paper, we compare the biological effects of both mesoporous silica nanoparticles extracted from Urtica dioica L. and pyrogenic material. Both SEM and TEM investigations confirmed the size range of tested nanoparticles was between 6 and 20 nanometers and their amorphous structure. The cytotoxic activity of the compounds and intracellular ROS were determined in relation to cells HMEC-1 and erythrocytes. The cytotoxic effects of SiO2 NPs were determined after exposure to different concentrations and three periods of incubation. The same effects for endothelial cells were tested under the same range of concentrations but after 2 and 24 h of exposure to erythrocytes. The cell viability was measured using spectrophotometric and fluorimetric assays, and the impact of the nanoparticles on the level of intracellular ROS. The obtained results indicated that bioSiO2 NPs, present higher toxicity than pyrogenic NPs and have a higher influence on ROS production. Mesoporous silica nanoparticles show good hemocompatibility but after a 24 h incubation of erythrocytes with silica, the increase in hemolysis process, the decrease in osmotic resistance of red blood cells, and shape of erythrocytes changed were observed.
- MeSH
- endoteliální buňky účinky léků MeSH
- erytrocyty účinky léků MeSH
- hemolýza účinky léků MeSH
- lidé MeSH
- nanočástice aplikace a dávkování chemie MeSH
- oxid křemičitý aplikace a dávkování chemie MeSH
- oxidační stres účinky léků MeSH
- poréznost MeSH
- povrchové vlastnosti MeSH
- reaktivní formy kyslíku metabolismus MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.
- MeSH
- apoptóza MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mannany chemie metabolismus MeSH
- myši inbrední BALB C MeSH
- myši inbrední C3H MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory prsu metabolismus patologie MeSH
- nanočástice aplikace a dávkování chemie MeSH
- optické zobrazování MeSH
- proliferace buněk MeSH
- sentinelová uzlina metabolismus patologie MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Extensive exploitation of titanium dioxide nanoparticles (TiO2NPs) augments rapid release into the marine environment. When in contact with the body fluids of marine invertebrates, TiO2NPs undergo a transformation and adhere various organic molecules that shape a complex protein corona prior to contacting cells and tissues. To elucidate the potential extracellular signals that may be involved in the particle recognition by immune cells of the sea urchin Paracentrotus lividus, we investigated the behavior of TiO2NPs in contact with extracellular proteins in vitro. Our findings indicate that TiO2NPs are able to interact with sea urchin proteins in both cell-free and cell-conditioned media. The two-dimensional proteome analysis of the protein corona bound to TiO2NP revealed that negatively charged proteins bound preferentially to the particles. The main constituents shaping the sea urchin cell-conditioned TiO2NP protein corona were proteins involved in cellular adhesion (Pl-toposome, Pl-galectin-8, Pl-nectin) and cytoskeletal organization (actin and tubulin). Immune cells (phagocytes) aggregated TiO2NPs on the outer cell surface and within well-organized vesicles without eliciting harmful effects on the biological activities of the cells. Cells showed an active metabolism, no oxidative stress or caspase activation. These results provide a new level of understanding of the extracellular proteins involved in the immune-TiO2NP recognition and interaction in vitro, confirming that primary immune cell cultures from P. lividus can be an optional model for swift and efficient immune-toxicological investigations.
- MeSH
- buněčná adheze imunologie MeSH
- fagocyty imunologie MeSH
- galektiny imunologie MeSH
- glykoproteiny imunologie MeSH
- ježovky imunologie MeSH
- nanočástice aplikace a dávkování MeSH
- nektiny imunologie MeSH
- Paracentrotus imunologie MeSH
- proteinová korona imunologie MeSH
- proteom imunologie MeSH
- titan imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The ever increasing scenario of bacterial resistance against commonly available antibiotics is becoming a global threat of major concern, which necessitates the development of new strategies to overcome this hurdle. Conjugation of nanoparticles (NPs) with antimicrobial moieties, such as antibiotics, peptides or different biomolecules, has been one of the successful techniques in targeting antibiotic resistance. This review mainly focusses on the possible nanoparticle-drug conjugates with their activity against pathogenic bacterial infections. Nanoparticles play an array of roles, e.g. as a carrier, synergistically acting agent and as theranostic agent, henceforth facilitates the efficacy of therapy. Moreover, this review elaborates the studies with reported nanoparticles-drug conjugates that include their possible synthesis methodologies and applications. In most of the cases, the nanoparticles were found to increase the permeability of bacterial cell membrane, which enables higher uptake of antibiotics inside the bacterial cells which in return showed better effects. Even the conjugates were found to efficiently kill the antibiotic-resistant strains. Since several limitations are exerted by the biological systems, there is an urge for the advancement of nanoparticle-drug conjugates for better proficiency.
A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanocarrier control. An immunohistochemical analysis of the spinal cord tissue was performed at the end of the experiment and this proved a significant preservation of the white matter tissue, a reduced area of glial scaring and a higher amount of newly sprouted axons in the nanocurcumin treated group. The expression of endogenous genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, Nfkβ) and interleukins (IL-1β, TNF-α, IL-6, IL-12, CCL-5, IL-11, IL-10, IL-13) was evaluated by qPCR and showed changes in the expression of the inflammatory cytokines in the first two weeks after SCI.
- MeSH
- bílá hmota účinky léků metabolismus patologie MeSH
- jizva farmakoterapie metabolismus patologie MeSH
- krysa rodu rattus MeSH
- kurkumin aplikace a dávkování MeSH
- mediátory zánětu antagonisté a inhibitory metabolismus MeSH
- nanočástice aplikace a dávkování MeSH
- neuroglie účinky léků metabolismus patologie MeSH
- poranění míchy farmakoterapie metabolismus patologie MeSH
- potkani Wistar MeSH
- příprava léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate) (PGAS) are promising carriers for drug delivery. In order to investigate the impact of the particle interface characteristics on the biological fate, PGAS nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have similar particle sizes, but less negative zeta-potentials. Nanoparticles are double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676 (covalently bound to HPMA copolymer), and their biodistribution is investigated noninvasively by multispectral optical imaging. Both covalent and noncovalent coatings cause changes in the pharmacokinetics and biodistribution in healthy and tumor-bearing mice. In addition to the intended tumor accumulation, high signals of both fluorescent dyes are also observed in other organs, including liver, ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers needs further detailed and systematic investigations, especially with respect to the observed ovarian and adrenal gland accumulation.
- MeSH
- biologicky odbouratelné plasty chemie MeSH
- buňky HT-29 MeSH
- fluorescenční barviva chemie MeSH
- lidé MeSH
- methakryláty aplikace a dávkování chemie MeSH
- myši MeSH
- nádory farmakoterapie genetika patologie MeSH
- nanočástice aplikace a dávkování chemie MeSH
- nosiče léků aplikace a dávkování chemie MeSH
- polyestery aplikace a dávkování chemie MeSH
- systémy cílené aplikace léků * MeSH
- tkáňová distribuce účinky léků MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Evaluating nanoparticle (NP) toxicity in human cell systems is a fundamental requirement for future NP biomedical applications. In this study, we have designed a screening assay for assessing different types of cell death induced by NPs in human umbilical vein endothelial cell (HUVEC) culture. This assay consists of WST-8, LDH and Hoechst 33342 staining, all performed in one well, which enables an evaluation of cell viability, necrosis and apoptosis, respectively, in the same cell sample. The 96-well format and automated processing of fluorescent images enhances the assay rapidity and reproducibility. After testing the assay functionality with agents that induced different types of cell death, we investigated the endothelial toxicity of superparamagnetic iron oxide nanoparticles (SPIONs, 8 nm), silica nanoparticles (SiNPs, 7-14 nm) and carboxylated multiwall carbon nanotubes (CNTCOOHs, 60 nm). Our results indicated that all the tested NP types induced decreases in cell viability after 24 hours at a concentration of 100 μg/ml. SPIONs caused the lowest toxicity in HUVECs. By contrast, SiNPs induced pronounced necrosis and apoptosis. A time course experiment showed the gradual toxic effect of all the tested NPs. CNTCOOHs inhibited tetrazolium derivatives at 100 μg/ml, causing false negative results from the WST-8 and LDH assay. In summary, our data demonstrate that the presented "three-in-one" screening assay is capable of evaluating NP toxicity effectively and reliably. Due to its simultaneous utilization of two different methods to assess cell viability, this assay is also capable of revealing, if NPs interfere with tetrazolium salts.
- MeSH
- apoptóza účinky léků MeSH
- biotest MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- endoteliální buňky účinky léků MeSH
- lidé MeSH
- nanočástice aplikace a dávkování MeSH
- preklinické hodnocení léčiv metody MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Multimodal probes, which can be simultaneously visualized by multiple imaging modalities, enable the cellular uptake, intracellular fate, biodistribution and elimination to be tracked in organisms. In this study, we report the synthesis of crystalline WO3 and CaWO4 doped with Eu3+ or Tb3+ nanoparticles (size range of 10-160 nm) coated with polysaccharides, and these nanoparticles constitute a versatile easy-to-construct modular toolbox for multimodal imaging. The particles adsorb significant amounts of polysaccharides from the solution, providing biocompatibility and may serve as a platform for labeling. For WO3, the sorption is reversible. However, on CaWO4, stable coating is formed. CaWO4/Tb3+ coated with chemisorbed dextrin, mannan, guar gum and sodium alginate successfully underwent endocytosis with HepG2 cells and was visualized using confocal microscopy.
- MeSH
- biokompatibilní materiály chemie MeSH
- buňky Hep G2 MeSH
- endocytóza fyziologie MeSH
- konfokální mikroskopie MeSH
- lidé MeSH
- luminiscence * MeSH
- nanočástice aplikace a dávkování chemie účinky záření MeSH
- polysacharidy chemie MeSH
- terbium chemie MeSH
- wolfram chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
