This study presents a systematic comparison of the antifouling properties of water-soluble poly(2-oxazoline) (PAOx) and poly(2-oxazine) (PAOzi) brushes grafted to gold surfaces. PAOx and PAOzi are emerging polymer classes in biomedical sciences and are being considered superior alternatives to widely used polyethylene glycol (PEG). Four different polymers, poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx), poly(2-methyl-2-oxazine) (PMeOzi), and poly(2-ethyl-2-oxazine) (PEtOzi), each of them in three different chain lengths, are synthesized and characterized for their antifouling properties. Results show that all polymer-modified surfaces display better antifouling properties than bare gold surfaces as well as analogous PEG coatings. The antifouling properties increase in the following order: PEtOx < PMeOx ≈ PMeOzi < PEtOzi. The study suggests that the resistance to protein fouling derives from both surface hydrophilicity and the molecular structural flexibility of the polymer brushes. PEtOzi brushes with moderate hydrophilicity show the best antifouling performance, possibly due to their highest chain flexibility. Overall, the research contributes to the understanding of antifouling properties in PAOx and PAOzi polymers, with potential applications in various biomaterials.

• Klíčová slova
• antifouling coatings, poly(2-oxazine)s, poly(2-oxazoline)s, polymer brushes,
• MeSH
• bioznečištění * prevence a kontrola   MeSH
• oxaziny chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polymery * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oxaziny MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polyethylenglykoly MeSH
• polymery * MeSH

Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.

• MeSH
• biokompatibilní materiály chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• nosiče léků chemie   MeSH
• oxazoly chemická syntéza   chemie   MeSH
• polymery chemie   MeSH
• roztoky chemie   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• nosiče léků MeSH
• oxazoly MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polymery MeSH
• roztoky MeSH
• voda MeSH

Poly(2-alkyl-2-oxazoline)s (PAOx) represent a class of emerging polymers that can substitute or even outperform poly(ethylene oxide) (PEO) standard in various applications. Despite the great advances in PAOx research, there is still a gap in the direct experimental comparison of antifouling properties between PAOx and the golden standard PEO when exposed to blood. Motivated by this, we developed a straightforward protocol for the one-pot PAOx polymerization and surface coating by a "grafting to-" approach. First, we synthesized a library of hydrophilic poly(2-methyl-2-oxazoline)s (PMeOx) and poly(2-ethyl-2-oxazoline)s (PEtOx) with molar mass ranging from 1.5 to 10 kg/mol (DP = 16-115). The PAOx living chains were directly terminated by amine and hydroxyl groups of polydopamine (PDA) anchor layer providing the highest so far reported grafting densities ranging from 0.2 to 2.1 chains/nm2. In parallel, PEO chains providing the same degree of polymerization (molar mass from 1.2 to 5 kg/mol, DP = 28-116) bearing thiol groups were grafted to PDA. The thickness, surface-related parameters, covalent structure, and antifouling properties of the resulting polymer brushes were determined via various surface sensitive techniques. The comparison of the synthesized PAOx and PEO brushes led us to the conclusion that at the same surface-related parameters, PMeOx brushes show significantly better antifouling character when challenged against human blood plasma.

• MeSH
• hydrofobní a hydrofilní interakce účinky léků   MeSH
• krevní plazma účinky léků   MeSH
• lidé MeSH
• molekulová hmotnost MeSH
• oxazoly chemická syntéza   chemie   farmakologie   MeSH
• polyaminy chemická syntéza   chemie   farmakologie   MeSH
• polyethylenglykoly chemická syntéza   chemie   farmakologie   MeSH
• polymerizace MeSH
• polymery chemická syntéza   chemie   farmakologie   MeSH
• povrchové vlastnosti účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• oxazoly MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polyaminy MeSH
• polyethylenglykoly MeSH
• polymery MeSH

Herein, we describe a new method for the synthesis of superhydrophilic poly(2-alkyl-2-oxazoline)s (PAOx) from poly(2-ethyl-2-oxazoline) (PEtOx). A well-defined linear polyethylenimine was prepared from PEtOx by controlled acidic hydrolysis of its side-chains followed by reacylation with different carboxylic acids. Using this protocol, we obtained a series of new hydrophilic PAOx containing side-chain ether groups with potential in biomaterials science. The relative hydrophilicity of the polymers was assessed, revealing that poly(2-methoxymethyl-2-oxazoline) (PMeOMeOx) is the most hydrophilic PAOx reported to date. Additionally, the amorphous poly(2-methoxy-ethoxy-ethoxymethyl-2-oxazoline) (PDEGOx) shows the lowest reported glass transition temperature (-25 °C) within the PAOx family to date. The biomedical potential of the prepared polymers was further fortified by an in vitro cytotoxicity study, where all polymers appeared to be noncytotoxic. The described synthetic protocol is universal and can be extremely versatile, especially for PAOx that are difficult to prepare by conventional cationic ring-opening polymerization due to the monomer interference and/or degradation.

• MeSH
• HeLa buňky MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• oxazoly chemie   MeSH
• polyethylenimin chemie   MeSH
• tranzitní teplota MeSH
• vitrifikace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• oxazoly MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polyethylenimin MeSH

Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline-co-2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule. These polymers were successfully used to stabilize (solid) lipid nanoparticles ((S)LNP) consisting of tetradecan-1-ol and cholesterol with their hydrophobic anchor. While the pure polymers interacted with GLUT1-expressing cell lines mainly based on their physicochemical properties, especially via interactions of the hydrophobic anchor with membranous compartments of the cells, LNP-cell interactions hinted toward an influence of the glucosylation on particle-cell interactions. The presented LNP are therefore promising systems for the delivery of drugs into GLUT1-expressing cell lines.

• MeSH
• cholesterol chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• lipidy chemie   MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• oxazoly * chemie   MeSH
• polymery chemie   MeSH
• přenašeč glukosy typ 1 metabolismus   MeSH
• systémy cílené aplikace léků metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol MeSH
• lipidy MeSH
• nosiče léků MeSH
• oxazoly * MeSH
• poly(2-oxazoline) MeSH Prohlížeč
• polymery MeSH
• přenašeč glukosy typ 1 MeSH

We designed and synthesized a new delivery system for the anticancer drug doxorubicin based on a biocompatible hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) carrier with linear architecture and narrow molar mass distribution. The drug is connected to the polymer backbone via an acid-sensitive hydrazone linker, which allows its triggered release in the tumor. The in vitro studies demonstrate successful cellular uptake of conjugates followed by release of the cytostatic cargo. In vivo experiments in EL4 lymphoma bearing mice revealed prolonged blood circulation, increased tumor accumulation and enhanced antitumor efficacy of the PEtOx conjugate having higher molecular weight (40 kDa) compared to the lower molecular weight (20 kDa) polymer. Finally, the in vitro and in vivo anti-cancer properties of the prepared PEtOx conjugates were critically compared with those of the analogous system based on the well-established PHPMA carrier. Despite the relatively slower intracellular uptake of PEtOx conjugates, resulting also in their lower cytotoxicity, there are no substantial differences in in vivo biodistribution and anti-cancer efficacy of both classes of polymer-Dox conjugates. Considering the synthetic advantages of poly(2-alkyl-2-oxazoline)s, the presented study demonstrates their potential as a versatile alternative to well-known PEO- or PHPMA-based materials for construction of drug delivery systems.

• Klíčová slova
• Doxorubicin, Drug delivery, Hydrazone bond, Nanomedicine, Poly(2-oxazoline),
• MeSH
• akrylamidy chemie   MeSH
• doxorubicin chemie   terapeutické užití   MeSH
• HeLa buňky MeSH
• konfokální mikroskopie MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanomedicína metody   MeSH
• nosiče léků chemie   MeSH
• polyaminy chemie   MeSH
• polymery chemie   MeSH
• průtoková cytometrie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamidy MeSH
• doxorubicin MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků MeSH
• poly(2-ethyl-2-oxazoline) MeSH Prohlížeč
• polyaminy MeSH
• polymery MeSH

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.

• Klíčová slova
• biocompatibility, cell proliferation, fluorescence, functionalization of polymers, poly(2-isopropenyl-2-oxazoline), splenocytes,
• MeSH
• biokompatibilní materiály chemická syntéza   chemie   farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• buňky 3T3 MeSH
• endocytóza účinky léků   MeSH
• fibroblasty cytologie   MeSH
• fluorescenční spektrometrie MeSH
• imunomodulace účinky léků   MeSH
• konfokální mikroskopie MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• organely účinky léků   metabolismus   MeSH
• oxazoly chemická syntéza   chemie   farmakologie   MeSH
• polymery chemická syntéza   chemie   farmakologie   MeSH
• polypropyleny chemická syntéza   chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• slezina cytologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• oxazoly MeSH
• poly(2-isopropenyl-2-oxazoline) MeSH Prohlížeč
• polymery MeSH
• polypropyleny MeSH

This study focuses on developing surface coatings with excellent antifouling properties, crucial for applications in the medical, biological, and technical fields, for materials and devices in direct contact with living tissues and bodily fluids such as blood. This approach combines thermoresponsive poly(2-alkyl-2-oxazoline)s, known for their inherent protein-repellent characteristics, with established antifouling motifs based on betaines. The polymer framework is constructed from various monomer types, including a novel benzophenone-modified 2-oxazoline for photocrosslinking and an azide-functionalized 2-oxazoline, allowing subsequent modification with alkyne-substituted antifouling motifs through copper(I)-catalyzed azide-alkyne cycloaddition. From these polymers surface-attached networks are created on benzophenone-modified gold substrates via photocrosslinking, resulting in hydrogel coatings with several micrometers thickness when swollen with aqueous media. Given that poly(2-alkyl-2-oxazoline)s can exhibit a lower critical solution temperature in water, their temperature-dependent solubility is compared to the swelling behavior of the surface-attached hydrogels upon thermal stimulation. The antifouling performance of these hydrogel coatings in contact with human blood plasma is further evaluated by surface plasmon resonance and optical waveguide spectroscopy. All surfaces demonstrate extremely low retention of blood plasma components, even with undiluted plasma. Notably, hydrogel layers with sulfobetaine moieties allow efficient penetration by plasma components, which can then be easily removed by rinsing with buffer.

• Klíčová slova
• SPR/OWS, antifouling thermoresponsive hydrogel coatings, betaines, blood plasma, photocrosslinkable poly(2-oxazoline)s,
• MeSH
• alkyny MeSH
• azidy * MeSH
• benzofenony MeSH
• hydrogely * chemie   MeSH
• krevní plazma MeSH
• lidé MeSH
• polymery chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkyny MeSH
• azidy * MeSH
• benzofenony MeSH
• hydrogely * MeSH
• polymery MeSH

Amphiphilic gradient copolymers represent a promising alternative to extensively used block copolymers due to their facile one-step synthesis by statistical copolymerization of monomers of different reactivity. Herein, an in-depth analysis is provided of micelles based on amphiphilic gradient poly(2-oxazoline)s with different chain lengths to evaluate their potential for micellar drug delivery systems and compare them to the analogous diblock copolymer micelles. Size, morphology, and stability of self-assembled nanoparticles, loading of hydrophobic drug curcumin, as well as cytotoxicities of the prepared nanoformulations are examined using copoly(2-oxazoline)s with varying chain lengths and comonomer ratios. In addition to several interesting differences between the two copolymer architecture classes, such as more compact self-assembled structures with faster exchange dynamics for the gradient copolymers, it is concluded that gradient copolymers provide stable curcumin nanoformulations with comparable drug loadings to block copolymer systems and benefit from more straightforward copolymer synthesis. The study demonstrates the potential of amphiphilic gradient copolymers as a versatile platform for the synthesis of new polymer therapeutics.

• Klíčová slova
• gradient copolymers, nanomedicine, poly(2-oxazoline)s, self-assembly,
• MeSH
• hydrofobní a hydrofilní interakce MeSH
• kurkumin * chemie   MeSH
• micely * MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kurkumin * MeSH
• micely * MeSH
• nosiče léků MeSH
• polymery MeSH

MOTIVATION: Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target. HYPOTHESIS: We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation. EXPERIMENTS: In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering. FINDINGS: We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses.

• Klíčová slova
• Amyloid fibrils, Amyloidosis, Gradient copolymers, Lysozyme, Poly(2-oxazoline),
• MeSH
• amyloid * MeSH
• amyloidogenní proteiny MeSH
• amyloidóza * MeSH
• kalorimetrie MeSH
• lidé MeSH
• polymery MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloid * MeSH
• amyloidogenní proteiny MeSH
• polymery MeSH