Friederike Adams

In the context of green chemistry, replacing fossil‐based components with renewable alternatives in polymerization processes represents a key challenge towards more sustainable materials. This work establishes a terpene‐based polymerization system for the synthesis of aliphatic polyesters via yttrium‐mediated ring‐opening polymerization of bio‐based lactones. An aminoalkoxy bis(phenolate) yttrium catalyst was combined with terpene‐derived alcohols as nucleophiles and dl ‐limonene as a renewable solvent, replacing conventional systems based on isopropyl alcohol and toluene. The terpene‐based alcohols ( E )‐geraniol, (1 R ,2 S ,5 R )‐ l ‐menthol and (3 R )‐linalool, differing in steric demand and substitution pattern, were evaluated as initiators and chain transfer agents. Polymerizations of lactones with varying ring‐strain and size (β‐butyrolactone, ω‐pentadecalactone and the terpene‐derived (−)‐menthide) were performed and directly compared to fossil‐based reference systems. All monomers were successfully polymerized under fully terpene‐based conditions, yielding polymers with controllable molecular weights (3.2–44.6 kg mol ⁻¹ ), low dispersities ( Đ = 1.1–1.4) and defined end groups. Kinetic studies revealed a strong influence of nucleophile structure and concentration on polymerization characteristics, with increasing chain transfer agent content leading to decreased molecular weights, consistent with an immortal coordination‐insertion mechanism that can enable efficient catalyst utilization and reduced catalyst loadings. The fully terpene‐based systems provided comparable or improved control over the polymerization and end‐group analysis confirmed the incorporation of terpene‐derived initiating groups, enabling subsequent post‐polymerization functionalization via thiol‐ene chemistry. These results demonstrate that renewable nucleophiles and solvents can effectively replace fossil‐based components in rare‐earth metal‐catalyzed ring‐opening polymerization, providing access to sustainable and functionalizable aliphatic polyesters. © 2026 The Author(s). Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Mechanically interlocked molecules (MIMs) offer attractive opportunities to modularly integrate bioactivity, molecular recognition, and optical readout within a single supramolecular architecture. Here, we report a fluorescent [2]rotaxane platform based on a cationic organometallic pillarplex ring and fluorescein stoppers as intrinsic imaging labels. The pillarplex ring promotes interactions with biorelevant polyanions such as nucleic acids, while the fluorescein stoppers ensure optical traceability by confocal microscopy. Cellular uptake by A549 cancer cells is demonstrated, showing that the fluorescent rotaxane remains predominantly localized in the cytoplasm. The rotaxane can furthermore be integrated into multicomponent nanoassemblies, such as coacervates and biopharmaceutical-relevant polyplexes. For the latter, in the presence of siRNA and cationic polymers, the rotaxane forms assemblies that even enhance cellular uptake and imaging. Collectively, these findings demonstrate that dye incorporation provides a powerful strategy for modulating pillarplex rotaxanes, thereby enabling controlled uptake, localization within the cell by fluorescence labeling and co-assembly.

Owing the complex anatomy and multiple physiological barriers, delivering drugs to the posterior segment of the eye remains challenging. While intravitreal injection can improve drug delivery, the diffusion of therapeutics through the vitreous humor and their uptake by the retina remain limited due to the anionic nature of the vitreous humor, attributed to its collagen and glycosaminoglycan content. Poly(solketal acrylate)‐based nanoparticles (PSA‐NPs) were developed via single‐emulsion solvent evaporation and nanoprecipitation techniques and loaded with Nile red (NR‐PSA‐NPs) as a hydrophobic drug model, enabling in vitro and ex vivo tracking via fluorescence microscopy. These NPs exhibit a neutral to negative surface charge, enhancing their distribution through the vitreous humor. Evaluating these NPs for drug delivery, cytotoxicity studies using retinal cells confirmed their excellent nontoxic profiles. Additionally, fluorescence microscopy and FACS analysis revealed a significant increase in the uptake of NR‐PSA‐NPs in ARPE‐19 cells (human retinal pigment epithelial cell line) compared to that of free dye. Moreover, incubation of NR‐PSA‐NPs with retinal organ cultures and their intravitreal injection into whole porcine eyes showed red fluorescence across all retinal layers, confirming successful uptake, distribution, and widespread retinal penetration, making these NPs promising carriers for delivering hydrophobic drugs to the posterior eye segment.

Terpenes exhibit a wide range of structures, thus enabling diverse applications. Herein, (‐)‐menthide and trans (+)‐carvomenthide were synthesized from terpenoids (‐)‐menthone and (+)‐dihydrocarvone, differing solely in their substitution pattern. (‐)‐Menthide features a methyl group at position 4 and an isopropyl group at position 7, whereas (+)‐carvomenthide shows the inverse arrangement. Both lactones were transformed into polyesters via ring‐opening polymerization (ROP) using an amino‐alkoxy‐bis(phenolate) yttrium catalyst. Polymerization kinetics revealed first‐order behavior, with (+)‐carvomenthide polymerizing significantly faster than (‐)‐menthide, while (‐)‐menthide demonstrated a more controlled polymerization. Activation energies were 36.3 kJ mol⁻¹ for (+)‐carvomenthide and 40.8 kJ mol⁻¹ for (‐)‐menthide. The Gibbs free energy of activation confirmed the lower energy barrier for (+)‐carvomenthide polymerization, with experimental values of 81.9 kJ mol⁻¹ compared to 89.1 kJ mol⁻¹ for (‐)‐menthide. Density functional theory (DFT) calculations supported the experimental results, with computed Gibbs free energy barriers of 84.5 kJ mol⁻¹ for trans (+)‐carvomenthide and 82.3 kJ mol⁻¹ for (‐)‐menthide and mechanistic differences. Refined free energy barriers were determined to be 102.1 kJ mol^⁻1 for (‐)‐menthide and 84.9 kJ mol^⁻1 for trans (+)‐carvomenthide, agreeing with the experimental trend. These findings highlight the critical role of molecular structure and substituent position on polymerization kinetics and energy barriers in metal‐catalyzed polymerization.

Poly((−)-dihydrocarvide) is synthesized via yttrium-mediated ring-opening polymerization. Block copolymerization and functionalization yield semi-crystalline and brush polymers, highlighting its versatility in copolymer design.

Using phosphorus-containing, cationic polymers synthesized by REM-GTP, novel siRNA delivery agents were developed that demonstrate excellent siRNA encapsulation and efficient endosomal escape and gene silencing, while showing low cytotoxicity.

Ocular gene therapy targets eye diseases at the genetic level. Systemic transport of nucleic acids to ocular tissues poses a significant challenge, as the effectiveness of crossing the blood‐retina barrier limits nucleic acid penetration. Therefore, local administration, such as topical, periocular, or intraocular, can improve the outcome of in vivo gene therapy by bypassing the first‐pass effect and minimizing the systemic toxic effects. The eye is an immune‐privileged organ with limited local immune response, making it an ideal candidate for local gene therapy. Ocular gene therapy offers a promising solution for the treatment of a wide range of retinal diseases including age‐related macular degeneration, diabetic retinopathy, retinitis pigmentosa, and Leber congenital amaurosis. Gene therapy enables replacement of mutated genes essential for visual function, delivery of genes expressing neurotrophic factors and anti‐apoptosis factors for retinal degeneration, and delivery of genes expressing anti‐angiogenic proteins for ocular neovascularization. This perspective discusses the potential of nanoparticles for nucleic acid delivery to the retina, explores challenges, and evaluates different delivery methods, including non‐viral agents such as liposomes and polymers. These nonviral agents present advantages over traditional viral vectors, showing promise in overcoming limitations and offering a viable option for retinal gene therapy.

A controlled polymerization using activated acrylate monomers via ARGET-ATRP is developed with a tris[(4-dimethylamino pyridyl)methyl]amine ligand to address issues with weaker ligands and monomers that can undergo postpolymerization functionalization. This catalyst system enables the polymerization of N-acryloxy succinimide, fluorinated monomers, and isocyanato ethyl acrylate under controlled homogeneous conditions, ensuring linear molecular-weight growth and low polydispersity. Two block copolymerization strategies produce amphiphilic copolymers with narrow molecular-weight distributions and customizable compositions, allowing for various postpolymerization functionalizations.

After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our previous research, we found that spermine-based poly(β-amino ester)s are very promising for siRNA delivery. However, the role of hydrophobic modification in siRNA delivery of spermine-based poly(β-amino ester)s is not fully understood yet. In the current work, we synthesized spermine-based poly(β-amino ester)s with different percentages of oleylamine side chains, named P(SpOABAE). The chemical structures of the polymers were characterized by ¹H NMR. The polymers showed efficient siRNA encapsulation determined by SYBR Gold assays. The hydrodynamic diameters of the P(SpOABAE) polyplexes from charge ratio N/P 1 to 20 were 30-100 nm except for aggregation phenomena observed at N/P 3. Morphology of the polyplexes was visualized by atomic force microscopy, and cellular uptake was determined by flow cytometry in H1299 cells, where all the polyplexes showed significantly higher cellular uptake than hyperbranched polyethylenimine (25 kDa). The most hydrophobic P(SpOABAE) polyplexes were able to achieve more than 90% GFP knockdown in H1299/eGFP cells. The fact that gene silencing efficacy increased with hydrophobicity but cellular uptake was affected by both charge and hydrophobic interactions highlights the importance of endosomal escape. For pulmonary administration and improved storage stability, the polyplexes were spray-dried. Results confirmed the maintained siRNA activity after storage for 3 months at room temperature, indicating potential for dry powder inhalation.