Olga Kočková

We quantify unreacted resin leaching from SLA 3D-printed microfluidics: internal channels have higher leaching rates than external surfaces, standard light curing fails inside them, and no post-processing eliminates leaching entirely.

Dendrimers, constituting a prominent class of monodisperse and multivalent macromolecular compounds with outstanding properties, are characterized by regular and highly branched three-dimensional architectures and well-defined chemical structures. Within each structural type, the skeletal diversity is typically limited to the range of generations. Here, we introduce a novel modular synthetic strategy enabling an increase in the diversity of the dendrimer interior while maintaining its chemical nature. Resulting poly­(amide-carbosilane) (PAMCAS) dendrimers can be fine-tuned within one generation in terms of size, number, and density of end groups, as well as interior free volume. Using a tetravalent core and two building blocksdendritic wedges with branching degrees 3 and 6we demonstrate the potency of this strategy by producing a family of dendrimers through a controlled iterative process that combines highly chemoselective amidic coupling and thiol–ene click reaction (TEC). Within three generations, we prepared 14 structural analogs of PAMCAS dendrimers, systematically varying the order of building blocks and thus their structural profile. The solution properties of the obtained materials were studied by DLS, A4F, diffusion NMR, and molecular modeling. When using exclusively the AB₆ module, the dendritic growth is accelerated and allows straightforward access to structures with extremely high valency in a given generation. As the modular synthetic strategy poses a considerable purification challenge, we implemented organic solvent nanofiltration (OSN) as the main separation tool. Herein, we demonstrate proof-of-principle experiments to evaluate the scope and limits of the use of OSN as an effective separation method in synthetic macromolecular chemistry.

Photodynamic therapy (PDT) is a highly selective, clinically approved, minimally invasive technique that effectively eliminates cancer cells. Its effectiveness is limited by poor light penetration into tissue and the hydrophobic nature of photosensitizers, highlighting the need for new approaches to treatment. Here, a theranostic upconversion nanoplatform, consisting of a NaYF₄:Yb,Er,Tm,Fe core and a NaHoF₄ shell codoped with Yb, Nd, Gd and Tb ions, was designed to enhance PDT outcomes by integrating multi-wavelength upconversion luminescence, T₂-weighted magnetic resonance imaging (MRI) and PDT. The synthesized core–shell upconversion nanoparticles (CS-UCNPs) were coated with new verteporfin (VP)-conjugated alendronate-terminated poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate) [Ale-P(DMA-AEA)] grafted with poly(ethylene glycol) (PEG). Under 980 nm NIR irradiation, CS-UCNP@Ale-P(DMA-AEA)-PEG-VP nanoparticles generated reactive oxygen species (ROS) due to the efficient energy transfer between CS-UCNPs and VP. In a pilot preclinical study, intratumoral administration of nanoparticle conjugates to mice, followed by exposure to NIR light, induced necrosis of pancreatic tumor and suppressed its growth.

In the diagnostics of diabetes, specific targeting of drugs (e.g., liraglutide) to insulin-deficient β-cells with their simultaneous noninvasive imaging is currently needed. In this report, liraglutide (LGL)-conjugated poly(methyl vinyl ether-alt-maleic acid) (PMVEMA)-coated core-shell NaYF₄:Yb,Er,Fe@NaYF₄:Nd upconversion nanoparticles (CS-UCNPs) have been developed, thoroughly physicochemically characterized, and evaluated in vivo. Novel codoping of Fe²⁺, Yb³⁺, and Er³⁺ ions in the host NaYF₄ induced upconversion emission in the red region at both 980 and 808 nm excitation, making the particles suitable for deep-tissue imaging. Surface functionalization with PMVEMA provided colloidal stability and facilitated covalent conjugation with LGL, enabling targeted binding to GLP-1 receptors on pancreatic β-cells, increasing glucose-stimulated insulin secretion from isolated Langerhans islets. Biocompatibility of CS-UCNP@PMVEMA-LGL nanoparticles was confirmed by the trypan blue dye exclusion assay. When the fluorescent dye Flamma was conjugated to the nanoparticles, in vivo fluorescence imaging revealed significantly enhanced accumulation of CS-UCNP@PMVEMA-LGL-Flamma nanoparticles in the pancreas 24 h after intramuscular injection compared with intravenous administration, with luminescence intensity approximately doubled. The improved pancreatic targeting efficiency was attributed to enhanced binding to GLP-1 receptors. Confocal microscopy and elemental analysis confirmed receptor-mediated uptake of the nanoparticles by internalization and their localization within pancreatic β-cells. These findings highlight the potential of CS-UCNP@PMVEMA-LGL nanoparticles as biocompatible targetable imaging agents with future applications in pancreatic diagnostics.

In the article the possible using of low methylated amidated pectin for hydrogel bioinks preparation was investigated. The used pectins were obtained from different fruits and were characterized by their varying molecular weight characteristics, monosaccharide composition, and degree of esterification, degree of amidation and type of sugar additive (sucrose or glucose). The focus was on analysing the influence of the polymer structure and added sugar type on the 3D printability and thermal properties of the developed formulations. The studies had shown that the influence of the type and amount of sugar seems to be more crucial. It was observed that in the presence of sucrose, pectin crosslinking occurs not only through ionic and hydrogen interactions sugar-pectin-metal ion, but also through chemical crosslinking occurring as a result of the Millard reaction between amidated pectin and fructose formed as a result of sucrose hydrolysis. This phenomenon is not observed in the presence of glucose in the system, where the polymer forms reversible gels. The printability tests indicates that in order to obtain inks based on amidated pectin with a low degree of esterification, it is beneficial to use biopolymer standardized with glucose and optimize its amount in the system.

Here, we present the synthesis of diblock copolymers of poly(ethylene glycol) methyl ether-b-poly(ε-caprolactone) (mPEG-b-PCL) with prop-2-ynyl (propargyl) substituents on ε-caprolactone (ε-CL) units. The copolymerization of ε-CL with its propargylated derivative initiated by mPEG, followed by a thiol–yne click reaction with 1-thioglycerol, results in copolymers featuring vicinal diols capable of reversibly binding boronic acid derivatives. Detailed kinetic experiments were conducted to monitor the homo- and copolymerization of ε-CL with 7-(prop-2-ynyl)oxepan-2-one. By analyzing the kinetic data, we calculated the copolymerization parameters and mapped the composition profile of the resulting copolymers. The resulting gradient copolymers exhibited a lightly tapered composition profile, with an increase in ε-CL consumption at higher conversions where the more reactive 7-(prop-2-ynyl)oxepan-2-one is almost depleted. These findings were further validated through quantum chemical calculations, providing insights into the precise structure and composition of the copolymers. Characterization of the self-assembled nanoparticles was performed using static and dynamic light scattering, and their morphology was visualized via conventional and cryogenic transmission electron microscopy, confirming the formation of small, homogeneous spherical micelles. To demonstrate their potential in drug delivery, we combined a model drug consisting of a phenylboronic acid-conjugated metallacarborane cluster with diblock copolymer, utilizing reversible bonding between diols and phenylboronic acid and investigated the impact of drug loading on nanoparticle properties. Our comprehensive study underscores the importance of precise synthesis and structural prediction in the development of biodegradable diblock copolymers, offering valuable insights into their synthesis, kinetic behavior, and nanoscale assembly for advanced drug delivery applications.

Poly(2‐( N , N ‐dimethylamino)ethyl acrylate) (PDMAEA) is a promising charge‐shifting polycation with the capacity to form a range of morphologically distinct polyelectrolyte assemblies. Nevertheless, the basic character of the monomer and its hydrolytic instability impedes its controlled synthesis to higher molecular weight (MW). Herein, the reversible addition‐fragmentation chain transfer polymerization of DMAEA is reported using a tert‐butanol/V70 initiator/trithiocarbonate‐based chain transfer agent (CTA) polymerization setup. The CTA instability is demonstrated in the presence of the unprotonated tertiary amino group of the DMAEA monomer, which limits the control over the conversion and MW of the polymer. In contrast, the shielding of the amino groups by their protonation leads to polymerization with high conversions and excellent control over MWs of polymer up to 100 000 g mol ⁻¹ . Hydrolytic degradation study at pH values ranging from 5 to 9 reveals that both basic and protonated PDMAEA undergo a pH‐dependent hydrolysis. The proposed polymerization conditions provide a means of synthesizing PDMAEA with well‐controlled characteristics, which are beneficial for controlling the complexation processes during the formation of various polyelectrolyte assemblies.