Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.

• MeSH
• aminy chemie   MeSH
• antibakteriální látky farmakologie   MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• Bacteria účinky léků   MeSH
• bakteriální infekce farmakoterapie   etiologie   MeSH
• biofilmy účinky léků   MeSH
• COVID-19 MeSH
• HEK293 buňky účinky léků   MeSH
• hojení ran účinky léků   MeSH
• kationty farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence účinky léků   MeSH
• myši MeSH
• polymery chemie   farmakologie   MeSH
• popálení komplikace   MeSH
• reagencia zkříženě vázaná MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Combined experimental and computational studies of lipid membranes and liposomes, with the aim to attain mechanistic understanding, result in a synergy that makes possible the rational design of liposomal drug delivery system (LDS) based therapies. The LDS is the leading form of nanoscale drug delivery platform, an avenue in drug research, known as "nanomedicine", that holds the promise to transcend the current paradigm of drug development that has led to diminishing returns. Unfortunately this field of research has, so far, been far more successful in generating publications than new drug therapies. This partly results from the trial and error based methodologies used. We discuss experimental techniques capable of obtaining mechanistic insight into LDS structure and behavior. Insight obtained purely experimentally is, however, limited; computational modeling using molecular dynamics simulation can provide insight not otherwise available. We review computational research, that makes use of the multiscale modeling paradigm, simulating the phospholipid membrane with all atom resolution and the entire liposome with coarse grained models. We discuss in greater detail the computational modeling of liposome PEGylation. Overall, we wish to convey the power that lies in the combined use of experimental and computational methodologies; we hope to provide a roadmap for the rational design of LDS based therapies. Computational modeling is able to provide mechanistic insight that explains the context of experimental results and can also take the lead and inspire new directions for experimental research into LDS development. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

• MeSH
• lékové transportní systémy * MeSH
• lipidové dvojvrstvy chemie   MeSH
• liposomy * MeSH
• membránové lipidy chemie   MeSH
• mikrorovnovážné techniky křemenného krystalu MeSH
• polyethylenglykoly MeSH
• radiační rozptyl MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

We report experimental results on damage induced by ionizing radiation to DNA origami triangles which are commonly used prototypes for scaffolded DNA origami nanostructures. We demonstrate extreme stability of DNA origami upon irradiation, which is caused by (i) the multi-row design holding the shape of the origami even after severe damage to the scaffold DNA and (ii) the reduction of damage to the scaffold DNA due to the protective effect of the folded structure. With respect to damage induced by ionizing radiation, the protective effect of the structure is superior to that of a naturally paired DNA double helix. Present results allow estimating the stability of scaffolded DNA origami nanostructures in applications such as nanotechnology, pharmacy or in singulo molecular studies where they are exposed to ionizing radiation from natural and artificial sources. Additionally, possibilities are opened for scaffolded DNA use in the design of radiation-resistant and radio-sensitive materials.

• MeSH
• DNA MeSH
• ionizující záření MeSH
• konformace nukleové kyseliny MeSH
• nanostruktury * MeSH
• nanotechnologie MeSH
• Publikační typ
• časopisecké články MeSH

Here, we describe a novel polymer platform suitable for efficient diagnostics and potential theranostics based on 89Zr-labeled N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugates. A set of polymers differing in molecular weight with either low dispersity or high dispersity were designed and synthesized and their biodistribution in vivo was successfully and precisely observed over 72 h. Moreover, the feasibility of two imaging techniques, fluorescence imaging (FI) and positron emission tomography (PET), was compared using labeled polymer conjugates. Both methods gave comparable results thus showing the enhanced diagnostic potential of the prepared polymer-dye or polymer-chelator-89Zr constructs. The in vivo and ex vivo PET/FI studies indicated that the dispersity and molecular weight of the linear HPMA polymers have a significant influence on the pharmacokinetics of the polymer conjugates. The higher molecular weight and narrower distribution of molecular weights of the polymer carriers improve their pharmacokinetic profile for highly prolonged blood circulation and enhanced tumor uptake. Moreover, the same polymer carrier with the anticancer drug doxorubicin bound by a pH-sensitive hydrazone bond showed higher cytotoxicity and cellular uptake in vitro. Therefore, HPMA copolymers with low dispersity and a molecular weight near the limit of renal filtration can be used as highly efficient polymer carriers of tumor-targeted therapeutics or for theranostics with minimal side effects.

• MeSH
• doxorubicin aplikace a dávkování   farmakokinetika   MeSH
• experimentální nádory * diagnostické zobrazování   farmakoterapie   MeSH
• Jurkat buňky MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků * chemie   MeSH
• optické zobrazování * MeSH
• polymery * chemie   MeSH
• pozitronová emisní tomografie * MeSH
• radionuklidy MeSH
• teranostická nanomedicína * MeSH
• tkáňová distribuce MeSH
• zirkonium MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

• Klíčová slova
• nanomedicína,
• MeSH
• biomedicínské inženýrství MeSH
• nanostruktury toxicita   využití   MeSH
• nanotechnologie metody   MeSH
• terapeutické užití MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Publikační typ
• monografie

Polysaccharide nanoparticles are promising materials in the wide range of disciplines such as medicine, nutrition, food production, agriculture, material science and others. They excel not only in their non-toxicity and biodegradability but also in their easy preparation. As well as inorganic particles, a protein corona (PC) around polysaccharide nanoparticles is formed in biofluids. Moreover, it has been considered that the overall response of the organism to nanoparticles presence depends on the PC. This review summarises scientific publications about the structural chemistry of polysaccharide nanoparticles and their impact on theranostic applications. Three strategies of implementation of the PC in theranostics have been discussed: I) Utilisation of the PC in therapy; II) How the composition of the PC is analysed for specific disease markers; III) How the formed PC can interact with the immune system and enhances the immunomodulation or immunoelimination. Thus, the findings from this review can contribute to improve the design of drug delivery systems. However, it is still necessary to elucidate the mechanisms of nano-bio interactions and discover new connections in nanoscale research.

• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• ateroskleróza diagnostické zobrazování   MeSH
• biologické markery analýza   MeSH
• humorální imunita účinky léků   MeSH
• lidé MeSH
• nádory diagnostické zobrazování   MeSH
• nanočástice chemie   terapeutické užití   MeSH
• polysacharidy chemie   terapeutické užití   MeSH
• proteinová korona * imunologie   MeSH
• teranostická nanomedicína metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We developed membrane voltage nanosensors that are based on inorganic semiconductor nanoparticles. We provide here a feasibility study for their utilization. We use a rationally designed peptide to functionalize the nanosensors, imparting them with the ability to self-insert into a lipid membrane with a desired orientation. Once inserted, these nanosensors could sense membrane potential via the quantum confined Stark effect, with a single-particle sensitivity. With further improvements, these nanosensors could potentially be used for simultaneous recording of action potentials from multiple neurons in a large field of view over a long duration and for recording electrical signals on the nanoscale, such as across one synapse.

• MeSH
• biosenzitivní techniky metody   MeSH
• elektřina * MeSH
• HEK293 buňky MeSH
• kvantové tečky chemie   MeSH
• lidé MeSH
• membránové potenciály fyziologie   MeSH
• nanotrubičky ultrastruktura   MeSH
• povrchové vlastnosti MeSH
• studie proveditelnosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

Kinesin is a biological molecular nanomotor which converts chemical energy into mechanical work. To fulfill various nanotechnological tasks in engineered environments, the function of biological molecular motors can be altered by artificial chemical modifications. The drawback of this approach is the necessity of designing and creating a new motor construct for every new task. We propose that intense nanosecond-scale pulsed electric field could modify the function of nanomotors. To explore this hypothesis, we performed molecular dynamics simulation of a kinesin motor domain docked on a subunit of its microtubule track - a single tubulin heterodimer. In the simulation, we exposed the kinesin motor domain to intense (100 MV/m) electric field up to 30 ns. We found that both the magnitude and angle of the kinesin dipole moment are affected. Furthermore, we found that the electric field affects contact surface area between kinesin and tubulin, the structure and dynamics of the functionally important kinesin segments, including microtubule binding motifs as well as nucleotide hydrolysis site which power the nanomotor. These findings indicate that external intense nanosecond-scale electric field could alter kinesin behavior. Our results contribute to developing novel electromagnetic methods for modulating the function of biomolecular matter at the nanoscale.

• MeSH
• časové faktory MeSH
• elektřina * MeSH
• kineziny chemie   metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• simulace molekulární dynamiky * MeSH
• tubulin metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Micro/nanomotors are nanoscale devices that have been explored in various fields, such as drug delivery, environmental remediation, or biosensing and diagnosis. The use of micro/nanomotors has grown considerably over the past few years, partially because of the advantages that they offer in the development of new conceptual avenues in biosensing. This is due to their propulsion and intermixing in solution compared with their respective static forms, which enables motion-based detection methods and/or decreases bioassay time. This review focuses on the impacts of micro/nanomotors on biosensing research in the last 2 years. An overview of designs for bioreceptor attachment to micro/nanomotors is given. Recent developments have focused on chemically propelled micromotors using external fuels, commonly hydrogen peroxide. However, the associated fuel toxicity and inconvenience of use in relevant biological samples such as blood have prompted researchers to explore new micro/nanomotor biosensing approaches based on biocompatible propulsion sources such as magnetic or ultrasound fields. The main advances in biocompatible propulsion sources for micro/nanomotors as novel biosensing platforms are discussed and grouped by their propulsion-driven forces. The relevant analytical applications are discussed and representatively illustrated. Moreover, envisioning future biosensing applications, the principal advantages of micro/nanomotor synthesis using biocompatible and biodegradable materials are given. The review concludes with a realistic drawing on the present and future perspectives.

• MeSH
• lékové transportní systémy MeSH
• nanostruktury * MeSH
• nanotechnologie metody   MeSH
• peroxid vodíku MeSH
• regenerace a remediace životního prostředí * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The high specific surface area and high reactivity of nanoscale zero-valent iron (nZVI) particles have led to much research on their application to environmental remediation. The reactivity of nZVI is affected by both the water chemistry and the properties of the particular type of nZVI particle used. We have investigated the reactivity of three types of commercially available Nanofer particles (from Nanoiron, s.r.o., Czech Republic) that are currently either used in, or proposed for use in full scale environmental remediation projects. The performance of one of these, the air-stable and thus easy-to-handle Nanofer Star particle, has not previously been reported. Experiments were carried out first in batch shaking reactors in order to derive maximum reactivity rates and provide a rapid estimate of the Nanofer particle's reactivity. The experiments were performed under near-natural environmental conditions with respect to the pH value of water and solute concentrations, and results were compared with those obtained using synthetic water. Thereafter, the polyelectrolyte-coated Nanofer 25S particles (having the highest potential for transport within porous media) were chosen for the experiments in column reactors, in order to elucidate nanoparticle reactivity under a more field-site realistic setting. Iopromide was rapidly dehalogenated by the investigated nZVI particles, following pseudo-first-order reaction kinetics that was independent of the experimental conditions. The specific surface area normalized reaction rate constant (kSA) value in the batch reactors ranged between 0.12 and 0.53Lm(-2)h(-1); it was highest for the uncoated Nanofer 25 particles, followed by the polyacrylic acid-coated Nanofer 25S and air-stable Nanofer Star particles. In the batch reactors all particles were less reactive in natural water than in synthetic water. The kSA values derived from the column reactor experiments were about 1000 times lower than those from the batch reactors, ranging between 2.6×10(-4) and 5.7×10(-4)Lm(-2)h(-1). Our results revealed that the easy-to-handle and air-stable Nanofer Star particles are the least reactive of all the Nanofer products tested. The reaction kinetics predicted by column experiments were more realistic than those predicted by batch experiments and these should therefore be used when designing a full-scale field application of nanomaterials for environmental remediation.

• MeSH
• akrylové pryskyřice chemie   MeSH
• johexol analogy a deriváty   chemie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• nanočástice chemie   MeSH
• poréznost MeSH
• regenerace a remediace životního prostředí MeSH
• voda chemie   MeSH
• železo chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH