Multidrug resistance (MDR) represents one of the major concerns in cancer therapy as it may cause reduced efficacy of chemotherapeutic drugs due to the overexpression of ABC transporters, particularly P-glycoprotein (P-gp). This study explores the potential of novel amphiphilic diblock (DB) copolymers composed of poly[N-(2-hydroxypropyl)methacrylamide]-based copolymers (PHPMA) and poly(propylene oxide) (PPO) to overcome MDR mechanisms. The DB copolymers and their doxorubicin (Dox) conjugates significantly increased Dox accumulation in P-gp positive cells, markedly sensitizing them to Dox cytotoxic activity. The underlying mechanisms included depletion of intracellular ATP with subsequent inhibition of P-gp mediated drug efflux, an altered mitochondrial membrane potential, and increased ROS production. Moreover, the DB-Dox conjugates inhibited tumor growth in vivo more effectively compared to the corresponding PHPMA-based drug delivery system. Copolymers with additionally loaded PPO in the micelle core demonstrated superior efficacy in terms of P-gp inhibition, ATP depletion, and chemosensitizing effect in vitro, as well as antitumor activity in vivo. DB copolymers effectively depleted ATP levels both in vitro and in vivo using patient-derived xenograft (PDX) models, underscoring their capacity to enhance the effectiveness of standard chemotherapy and translational potential.

• Klíčová slova
• Diblock copolymers, Drug delivery system, HPMA copolymer, Intracellular ATP depletion, Multidrug resistance, P-glycoprotein inhibition, PPO, Sensitization to chemotherapy,
• MeSH
• adenosintrifosfát metabolismus   MeSH
• chemorezistence účinky léků   MeSH
• doxorubicin * aplikace a dávkování   chemie   terapeutické užití   MeSH
• lidé MeSH
• methakryláty chemie   MeSH
• micely MeSH
• mnohočetná léková rezistence účinky léků   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• nosiče léků * chemie   MeSH
• P-glykoprotein * metabolismus   MeSH
• polymery chemie   MeSH
• polypropyleny * chemie   MeSH
• propylenglykoly * chemie   aplikace a dávkování   MeSH
• protinádorová antibiotika * aplikace a dávkování   chemie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH
• doxorubicin * MeSH
• methakryláty MeSH
• micely MeSH
• nosiče léků * MeSH
• P-glykoprotein * MeSH
• polymery MeSH
• polypropylene glycol MeSH Prohlížeč
• polypropyleny * MeSH
• propylenglykoly * MeSH
• protinádorová antibiotika * MeSH

Amphiphilic gradient copolymers are promising alternatives to block copolymers for self-assembled nanomaterials due to their straightforward synthesis via statistical copolymerization of monomers with different reactivities and hydrophilicity. By carefully selecting monomers, nanoparticles can be synthesized in a single step through gradient copolymerization-induced self-assembly (gPISA). We synthesized highly sensitive 19F MRI nanotracers via aqueous dispersion gPISA of hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMA) with core-forming N,N-(2,2,2-trifluoroethyl)acrylamide (TFEAM). The PPEGMA-grad-PTFEAM nanoparticles were optimized to achieve spherical morphology and exceptional 19F MRI performance. Noncytotoxicity was confirmed in Panc-1 cells. In vitro 19F MR relaxometry and imaging demonstrated their diagnostic imaging potential. Notably, these gradient copolymer nanotracers outperformed block copolymer analogs in 19F MRI performance due to their gradient architecture, enhancing 19F relaxivity. The synthetic versatility and superior 19F MRI performance of gradient copolymers highlight their potential in advanced diagnostic imaging applications.

• MeSH
• hydrofobní a hydrofilní interakce MeSH
• kontrastní látky chemie   chemická syntéza   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• methakryláty * chemie   MeSH
• nádorové buněčné linie MeSH
• nanočástice chemie   MeSH
• polyethylenglykoly * chemie   MeSH
• polymerizace MeSH
• polymery chemie   chemická syntéza   MeSH
• zobrazování fluorovou magnetickou rezonancí metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kontrastní látky MeSH
• methakryláty * MeSH
• polyethylene glycol methacrylate MeSH Prohlížeč
• polyethylenglykoly * MeSH
• polymery MeSH

Prevention of fouling from proteins in blood plasma attracts significant efforts, and great progress is made in identifying surface coatings that display antifouling properties. In particular, poly(ethylene glycol) (PEG) is widely used and dense PEG-like cylindrical brushes of poly[oligo(ethylene glycol) methacrylate] (poly(OEGMA)) can drastically reduce blood plasma fouling. Herein, a comprehensive study of the variation of blood plasma fouling on this surface, including the analysis of the composition of protein deposits on poly(OEGMA) coatings after contact with blood plasma from many different donors, is reported. Correlation between the plasma fouling behavior and protein deposit composition points to the activation of the complement system as the main culprit of dramatically increased and accelerated deposition of blood plasma proteins on this type of antifouling coating, specifically through the classical pathway. These findings are consistent with observations on PEGylated drug carriers and highlight the importance of understanding the potential interactions between antifouling coatings and their environment.

• Klíčová slova
• antifouling coatings, donor variability, mass spectrometry, polyethylene glycol, polymer brushes, protein adsorption, protein identification, surface plasmon resonance,
• MeSH
• biokompatibilní potahované materiály chemie   MeSH
• bioznečištění prevence a kontrola   MeSH
• krevní proteiny chemie   analýza   MeSH
• lidé MeSH
• methakryláty chemie   MeSH
• polyethylenglykoly * chemie   MeSH
• povrchové vlastnosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní potahované materiály MeSH
• krevní proteiny MeSH
• methakryláty MeSH
• polyethylenglykoly * MeSH

Bioinks play a crucial role in tissue engineering, influencing mechanical and chemical properties of the printed scaffold as well as the behavior of encapsulated cells. Recently, there has been a shift from animal origin materials to their synthetic alternatives. In this context, we present here bioinks based on fully synthetic and biodegradable poly(α,L-amino acids) (PolyAA) as an alternative to animal-based gelatin methacrylate (Gel-Ma) bioinks. Additionally, we first reported the possibility of the visible light photoinitiated incorporation of the bifunctional cell adhesive RGD peptide into the PolyAA hydrogel matrix. The obtained hydrogels are shown to be cytocompatible, and their mechanical properties closely resemble those of gelatin methacrylate-based scaffolds. Moreover, combining the unique properties of PolyAA-based bioinks, the photocrosslinking strategy, and the use of droplet-based printing allows the printing of constructs with high shape fidelity and structural integrity from low-viscosity bioinks without using any sacrificial components. Overall, presented PolyAA-based materials are a promising and versatile toolbox that extends the range of bioinks for droplet bioprinting.

• Klíčová slova
• adhesion-promoting peptide, bioprinting, hydrogels, lung fibroblasts, mesenchymal stem cells, photogelation,
• MeSH
• 3D tisk MeSH
• aminokyseliny * chemie   MeSH
• biokompatibilní materiály * chemie   MeSH
• bioprinting metody   MeSH
• hydrogely * chemie   MeSH
• inkoust MeSH
• lidé MeSH
• methakryláty chemie   MeSH
• myši MeSH
• oligopeptidy chemie   MeSH
• světlo * MeSH
• testování materiálů MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury * chemie   MeSH
• viskozita MeSH
• želatina * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny * MeSH
• arginyl-glycyl-aspartic acid MeSH Prohlížeč
• biokompatibilní materiály * MeSH
• hydrogely * MeSH
• methakryláty MeSH
• oligopeptidy MeSH
• želatina * MeSH

We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhibitors were synthesized to evaluate the anticancer effect of Dox and STAT3 inhibitor co-delivery into tumors. S3iD1-3 and their copolymer-bound counterparts (P-S3iD1-P-S3iD3) showed considerable in vitro cytostatic activities in five mouse and human cancer cell lines with IC50 ~0.6-7.9 μM and 0.7-10.9 μM, respectively. S3iD2 and S3iD3 were confirmed to inhibit the STAT3 signaling pathway. The combination of HPMA copolymer-bound Dox (P-Dox) and P-S3iD3 at the dosage showing negligible toxicity demonstrated significant antitumor activity in B16F10 melanoma-bearing mice and completely cured 2 out of 15 mice. P-Dox alone had a significantly lower therapeutic activity with no completely cured mice. Thus, polymer conjugates bearing STAT3 inhibitors may be used for the chemosensitization of chemorefractory tumors.

• Klíčová slova
• Doxorubicin, HPMA copolymer carrier, STAT3 inhibitor, pH-sensitive drug release,
• MeSH
• doxorubicin * farmakologie   terapeutické užití   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové MeSH
• lidé MeSH
• methakryláty * MeSH
• myši MeSH
• nádory * farmakoterapie   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin * MeSH
• hydroxypropyl methacrylate MeSH Prohlížeč
• kyseliny polymethakrylové MeSH
• methakryláty * MeSH
• STAT3 protein, human MeSH Prohlížeč
• transkripční faktor STAT3 MeSH

Gene silencing using small interfering RNAs (siRNAs) is a selective and promising approach for treatment of numerous diseases. However, broad applications of siRNAs are compromised by their low stability in a biological environment and limited ability to penetrate cells. Nanodiamonds (NDs) coated with cationic polymers can enable cellular delivery of siRNAs. Recently, we developed a new type of ND coating based on a random copolymer consisting of (2-dimethylaminoethyl) methacrylate (DMAEMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomers. These hybrid ND-polymer particles (Cop+-FND) provide near-infrared fluorescence, form stable complexes with siRNA in serum, show low toxicity, and effectively deliver siRNA into cells in vitro and in vivo. Here, we present data on the mechanism of cellular uptake and cell trafficking of Cop+-FND : siRNA complexes and their ability to selectively suppress mRNA levels, as well as their cytotoxicity, viability and colloidal stability. We identified clathrin-mediated endocytosis as the predominant entry mechanism for Cop+-FND : siRNA into U-2 OS human bone osteosarcoma cells, with a substantial fraction of Cop+-FND : siRNA following the lysosome pathway. Cop+-FND : siRNA potently inhibited the target GAPDH gene with negligible toxicity and sufficient colloidal stability. Based on our results, we suggest that Cop+-FND : siRNA can serve as a suitable in vivo delivery system for siRNA.

• MeSH
• ethylaminy * MeSH
• kationty MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• methakryláty * MeSH
• nádorové buněčné linie MeSH
• nanodiamanty * MeSH
• polymery * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-dimethylaminoethyl methacrylate MeSH Prohlížeč
• ethylaminy * MeSH
• kationty MeSH
• malá interferující RNA MeSH
• methakryláty * MeSH
• nanodiamanty * MeSH
• polymery * MeSH

We characterized thermally polymerized organo-silica hybrid monolithic capillaries to test their applicability in the gradient elution of peptides. We have used a single-pot approach utilizing 3-(methacryloyloxy)propyltrimethoxysilane (MPTMS), ethylene dimethacrylate (EDMA), and n-octadecyl methacrylate (ODM) as functional monomers. The organo-silica monolith containing MPTMS and EDMA was compared with the stationary phase prepared by adding ODM to the original polymerization mixture. Column prepared using a three-monomer system provided a lower accessible volume of flow-through pores, a higher proportion of mesopores, and higher efficiency. We utilized isocratic and gradient elution data to predict peak widths in gradient elution. Both protocols provided comparable results and can be used for peptide peak width prediction. However, applying gradient elution data for peak width prediction seems simpler. Finally, we tested the effect of gradient time on achievable peak capacity in the gradient elution of peptides with a column prepared with a three-monomer system providing a higher peak capacity. However, the performance of hybrid organo-silica monolithic stationary phases in gradient elution of peptides must be improved compared to other monolithic stationary phases. The limiting factor is column efficiency in highly aqueous mobile phases, which needs to be focused on.

• Klíčová slova
• gradient elution, hybrid organo-silica monoliths, kinetic analysis, peptides,
• MeSH
• methakryláty chemie   MeSH
• oxid křemičitý * chemie   MeSH
• peptidy * chemie   MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ethylene dimethacrylate MeSH Prohlížeč
• methakryláty MeSH
• oxid křemičitý * MeSH
• peptidy * MeSH
• voda MeSH

Self-assembled bilayer structures such as those produced from amphiphilic block copolymers (polymersomes) are potentially useful in a wide array of applications including the production of artificial cells and organelles, nanoreactors, and delivery systems. These constructs are of important fundamental interest, and they are also frequently considered toward advances in bionanotechnology and nanomedicine. In this framework, membrane permeability is perhaps the most important property of such functional materials. Having in mind these considerations, we herein report the manufacturing of intrinsically permeable polymersomes produced using block copolymers comprising poly[2-(diisopropylamino)-ethyl methacrylate] (PDPA) as the hydrophobic segment. Although being water insoluble at pH 7.4, its pKa(PDPA) ∼ 6.8 leads to the presence of a fraction of protonated amino groups close to the physiological pH, thus conducting the formation of relatively swollen hydrophobic segments. Rhodamine B-loaded vesicles demonstrated that this feature confers inherent permeability to the polymeric membrane, which can still be modulated to some extent by the solution pH. Indeed, even at higher pH values where the PDPA chains are fully deprotonated, the experiments demonstrate that the membranes remain permeable. While membrane permeability can be, for instance, regulated by introducing membrane proteins and DNA nanopores, examples of membrane-forming polymers with intrinsic permeability have been seldom reported so far, and the possibility to regulate the flow of chemicals in these compartments by tuning block copolymer features and ambient conditions is of due relevance. The permeable nature of PDPA membranes possibly applies to a wide array of small molecules, and these findings can in principle be translocated to a variety of disparate bio-related applications.

• MeSH
• methakryláty * chemie   MeSH
• nanomedicína MeSH
• nosiče léků chemie   MeSH
• permeabilita MeSH
• polymery * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methakryláty * MeSH
• nosiče léků MeSH
• polymery * MeSH

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

• Klíčová slova
• 31P magnetic resonance imaging, controlled polymerization, phosphorus-containing polymers, polymer probes,
• MeSH
• biokompatibilní materiály chemie   MeSH
• fosfor * MeSH
• fosforylcholin chemie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• methakryláty chemie   MeSH
• micely MeSH
• polymery * chemie   MeSH
• povrchové vlastnosti MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• fosfor * MeSH
• fosforylcholin MeSH
• kyseliny polymethakrylové MeSH
• methakryláty MeSH
• micely MeSH
• polymery * MeSH

Conductive hydrogels are polymeric materials that are promising for bioelectronic applications. In the present study, a complex based on sulfonic cryogels and poly(3,4-ethylenedioxythiophene) (PEDOT) was investigated as an example of a conductive hydrogel. Preparation of polyacrylate cryogels of various morphologies was carried out by cryotropic gelation of 3-sulfopropyl methacrylate and sulfobetaine methacrylate in the presence of functional comonomers (2-hydroxyethyl methacrylate and vinyl acetate). Polymerization of 3,4-ethylenedioxythiophene in the presence of several of the above cryogels occurred throughout the entire volume of each polyelectrolyte cryogel because of its porous structure. Structural features of cryogel@PEDOT complexes in relation to their electrochemical properties were investigated. It was shown that poly(3,4-ethylenedioxythiophene) of a linear conformation was formed in the presence of a cryogel based on sulfobetaine methacrylate, while minimum values of charge-transfer resistance were observed in those complexes, and electrochemical properties of the complexes did not depend on diffusion processes.

• Klíčová slova
• composite PEDOT@polyelectrolyte, electrochemical impedance spectroscopy, polyelectrolyte gels,
• MeSH
• kryogely * chemie   MeSH
• methakryláty * chemie   MeSH
• polyelektrolyty MeSH
• polymerizace MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3,4-ethylenedioxythiophene MeSH Prohlížeč
• kryogely * MeSH
• methakryláty * MeSH
• polyelektrolyty MeSH
• sulfobetaine MeSH Prohlížeč