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
Inspired by the responsiveness of natural systems to their surrounding environments, researchers have sought to understand these biological processes and to develop functional stimuli-responsive polymeric systems for a wide range of applications such as drug delivery, imaging, and regenerative medicine. Both synthetic polymers and biopolymers have been studied and incorporated into assemblies of different morphologies as well as hydrogels with diverse shapes and dimensions. This special issue highlights recent research advances in this area, as well as exciting challenges to be tackled in the upcoming years.
The extracellular matrix (ECM) plays a crucial role in organoid cultures by supporting cell proliferation and differentiation. A key feature of the ECM is its mechanical influence on the surrounding cells, directly affecting their behavior. Matrigel, the most commonly used ECM, is limited by its animal-derived origin, batch variability, and uncontrollable mechanical properties, restricting its use in 3D cell-model-based mechanobiological studies. Poly(2-alkyl-2-oxazoline) (PAOx) synthetic hydrogels represent an appealing alternative because of their reproducibility and versatile chemistry, enabling tuning of hydrogel stiffness and functionalization. Here, we studied PAOx hydrogels with differing compressive moduli for their potential to support 3D cell growth. PAOx hydrogels support spheroid and organoid growth over several days without the addition of ECM components. Furthermore, we discovered intestinal organoid epithelial polarity reversion in PAOx hydrogels and demonstrate how the tunable mechanical properties of PAOx can be used to study effects on the morphology and oxygenation of live multicellular spheroids.
- Publikační typ
- časopisecké články 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
Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.6-4.9 μM) and form stable and uniform micelles 6-12 nm in diameter, depending on dendron shape; the results correlate well with molecular dynamics simulations. The compounds show relatively high cytotoxicity (IC50 1.2-21.0 μM) associated with micelle formation and inversely related to the size of assembled particles. Depending on their shape, the dendrons show promising results in terms of dendriplex formation and antibacterial activity. In addition to simple amphiphilic dendrons, a fluorescently labeled analogue was also prepared and utilized as an additive visualizing the dendron's cellular uptake.
- MeSH
- antibakteriální látky farmakologie chemie chemická syntéza MeSH
- dendrimery * chemie chemická syntéza farmakologie MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- micely * MeSH
- organofosforové sloučeniny * chemie MeSH
- povrchově aktivní látky chemie chemická syntéza farmakologie MeSH
- silany chemie MeSH
- simulace molekulární dynamiky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- carbosilane MeSH Prohlížeč
- dendrimery * MeSH
- micely * MeSH
- organofosforové sloučeniny * MeSH
- povrchově aktivní látky MeSH
- silany MeSH
Fibrotic changes in pediatric clubfoot provide an opportunity to improve corrective therapy and prevent relapses with targeted drugs. This study defines the parameters of clubfoot fibrosis and presents a unique analysis of a simple pseudo-3D in vitro model for disease-specific high-throughput drug screening experiments. The model combines clubfoot-derived fibroblasts with a biomimetic cultivation environment induced by the water-soluble polymers Ficoll and Polyvinylpyrrolidone, utilizing the principle of macromolecular crowding. We achieved higher conversion of soluble collagen into insoluble collagen, accelerated formation of the extracellular matrix layer and upregulated fibrosis-related genes in the mixed Ficoll environment. To test the model, we evaluated the effect of a potential antifibrotic drug, minoxidil, emphasizing collagen content and cross-linking. While the model amplified overall collagen deposition, minoxidil effectively blocked the expression of lysyl hydroxylases, which are responsible for the increased occurrence of specific collagen cross-linking in various fibrotic tissues. This limited the formation of collagen cross-link in both the model and control environments. Our findings provide a tool for expanding preclinical research for clubfoot and similar fibroproliferative conditions.
- MeSH
- biomimetika metody MeSH
- extracelulární matrix metabolismus účinky léků MeSH
- fibroblasty * metabolismus účinky léků MeSH
- fibróza * farmakoterapie MeSH
- kolagen * metabolismus chemie MeSH
- kultivované buňky MeSH
- lidé MeSH
- pes equinovarus * metabolismus farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kolagen * MeSH
The legislature determines the recycled and waste contents in fabrication processes to ensure more sustainable production. PLA's mechanical recycling and reuse are limited due to the performance decrease caused by thermal or hydrolytic instability. Our concept introduces an upcycling route involving PLA depolymerization using propylene glycol as a reactant, followed by the methacrylation, assuring the liquid systems' curability provided by radical polymerization. PLA-containing curable systems were studied from a rheological and thermomechanical viewpoint. The viscosity levels varied from 33 to 3911 mPa·s at 30 °C, giving a wide capability potential. The best system reached 2240 MPa storage modulus, 164.1 °C glass-transition temperature, and 145.6 °C heat-resistant index, competitive values to commercial systems. The printability was verified for all of the systems. Eventually, our concept led to SLA resin production containing PLA waste content up to 51 wt %.
- MeSH
- 3D tisk * MeSH
- esterifikace MeSH
- polyestery * chemie MeSH
- polymerizace MeSH
- reologie MeSH
- stereolitografie MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- poly(lactide) MeSH Prohlížeč
- polyestery * MeSH
There has been growing interest in polymeric systems that break down or undergo property changes in response to stimuli. Such polymers can play important roles in biological systems, where they can be used to control the release of therapeutics, modulate imaging signals, actuate movement, or direct the growth of cells. In this Perspective, after discussing the most important stimuli relevant to biological applications, we will present a selection of recent exciting developments. The growing importance of stimuli-responsive polysaccharides will be discussed, followed by a variety of stimuli-responsive polymeric systems for the delivery of small molecule drugs and nucleic acids. Switchable polymers for the emerging area of therapeutic response measurement in theranostics will be described. Then, the diverse functions that can be achieved using hydrogels cross-linked covalently, as well as by various dynamic approaches will be presented. Finally, we will discuss some of the challenges and future perspectives for the field.
- MeSH
- chytré polymery * chemie MeSH
- hydrogely * chemie MeSH
- lidé MeSH
- polymery chemie MeSH
- polysacharidy chemie MeSH
- systémy cílené aplikace léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chytré polymery * MeSH
- hydrogely * MeSH
- polymery MeSH
- polysacharidy MeSH
Photodynamic therapy (PDT) has the potential to cure pancreatic cancer with minimal side effects. Visible wavelengths are primarily used to activate hydrophobic photosensitizers, but in clinical practice, these wavelengths do not sufficiently penetrate deeper localized tumor cells. In this work, NaYF4:Yb3+,Er3+,Fe2+ upconversion nanoparticles (UCNPs) were coated with polymer and labeled with meta-tetra(hydroxyphenyl)chlorin (mTHPC; temoporfin) to enable near-infrared light (NIR)-triggered PDT of pancreatic cancer. The coating consisted of alendronate-terminated poly[N,N-dimethylacrylamide-co-2-aminoethylacrylamide]-graft-poly(ethylene glycol) [P(DMA-AEM)-PEG-Ale] to ensure the chemical and colloidal stability of the particles in aqueous physiological fluids, thereby also improving the therapeutic efficacy. The designed particles were well tolerated by the human pancreatic adenocarcinoma cell lines CAPAN-2, PANC-1, and PA-TU-8902. After intratumoral injection of mTHPC-conjugated polymer-coated UCNPs and subsequent exposure to 980 nm NIR light, excellent PDT efficacy was achieved in tumor-bearing mice.
- MeSH
- akrylamidy chemie MeSH
- fotochemoterapie * metody MeSH
- fotosenzibilizující látky * chemie farmakologie MeSH
- infračervené záření MeSH
- koloidy chemie MeSH
- lidé MeSH
- mesoporfyriny * chemie farmakologie MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní * farmakoterapie patologie MeSH
- nanočástice chemie MeSH
- polyethylenglykoly * chemie MeSH
- polymery chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- fotosenzibilizující látky * MeSH
- koloidy MeSH
- mesoporfyriny * MeSH
- polyethylenglykoly * MeSH
- polymery MeSH
- temoporfin MeSH Prohlížeč
Emerging material interest in bioelectronic applications has highlighted natural melanin and its derivatives as promising alternatives to conventional synthetic conductors. These materials, traditionally noted for their adhesive, antioxidant, biocompatible, and biodegradable properties, have barely been used as conductors due to their extremely low electrical activities. However, recent studies have demonstrated good conductive properties in melanin materials that promote electronic-ionic hybrid charge transfer, attributed to the formation of an extended conjugated backbone. This review examines the multifunctional properties of melanin materials, focusing on their chemical and electrochemical synthesis and their resulting structure-property-function relationship. The wide range of bioelectronic applications will also be presented to highlight their importance and potential to expand into new design concepts for high-performance electronic functional materials. The review concludes by addressing the current challenges in utilizing melanin for biodegradable bioelectronics, providing a perspective on future developments.
- MeSH
- biokompatibilní materiály * chemie MeSH
- elektrická vodivost MeSH
- elektronika MeSH
- lidé MeSH
- melaniny * chemie chemická syntéza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- biokompatibilní materiály * MeSH
- melaniny * MeSH
