Kristian Kempe

Poly(2-oxazoline) block copolymers (BCPs) have been demonstrated to undergo fully aqueous, heat-induced “living” seeded crystallization-driven self-assembly (CDSA) to form length-tunable nanorods. Due to their “stealthiness” and biocompatibility, these nanorods demonstrate potential as a drug delivery platform. However, research into drug loading and controlled release remains limited, and opportunities to exploit surface chemistry modification, including charged or other functional motifs, relatively unexplored. In this study, we synthesized poly(2-oxazoline-stat-ethylene imine) copolymers via preferential partial hydrolysis of poly(2-oxazoline) BCPs. These polymers were self-assembled via CDSA to form novel charged nanorods that retained morphology control and crystallinity similar to that of pure poly(2-oxazoline) BCPs. The dissolution kinetics of poly(2-oxazoline-stat-ethylene imine) nanorods showed that introducing secondary amines to the nanorod corona facilitated both temperature- and pH-responsive disassembly. These nanorods were confirmed to be biocompatible and seen to demonstrate an increase in cellular association, which correlated with higher cationic charge, alongside increased internalization toward multiple organelles, including lysosomes and endosomes.

This work demonstrates a synergistic drug delivery strategy integrating dual targeting, high payload loading, and controlled release, highlighting the potential of porous silicon nanoparticles for enhanced osteosarcoma therapy.

Stereochemistry is reported as a design parameter for modulating immune interactions of polymeric nanocarriers.

Lipid nanoparticles (LNPs) have rapidly emerged as the leading delivery platform for nucleic acid therapeutics due to their high encapsulation efficiency, scalable manufacturing, and clinical success in siRNA and mRNA medicines. Poly(ethylene glycol)‐lipids ((PEG)–lipids) have been central to this progress by providing steric stabilization, size control, and tunable biodistribution. However, PEGylation also introduces important limitations, including complement activation, pre‐existing and treatment‐induced anti‐PEG antibodies, and accelerated blood clearance, which increasingly constrain repeated and long‐term dosing strategies. This review focuses on recent advances in PEG‐alternative LNP designs, including non‐PEG polymers, zwitterionic and biomimetic lipids, polypeptides, and structurally modified PEG analogues. We compare how polymer chemistry, anchor geometry, and grafting architecture influence LNP formation, physicochemical properties, biodistribution, cellular uptake, and immunological outcomes. Moreover, we discuss key challenges that remain in translating PEG‐free and PEG‐modified LNPs toward clinical application and propose future directions to better understand in vivo behavior and enable rational design of next‐generation stealth LNPs. Overall, PEG lipid alternatives should not be viewed as simple PEG mimics, but as distinct surface‐engineering materials that create new nano‐bio interfaces and reshape LNP behavior in biological systems.

Chirality critically governs the pharmacodynamics and clinical performance of small molecule drugs, yet its role in governing bio-nano interactions of synthetic polymeric nanocarriers has remained largely unexplored. Surface grafting with hydrophilic, biocompatible “stealth” polymers such as poly(ethylene glycol) (PEG) is a critical design strategy for nanomedicines intended to reduce nonspecific biological interactions and achieve prolonged circulation. However, the rising prevalence of anti‑PEG antibodies has driven the search for fundamentally new design principles, mostly focused on substituting PEG with an entirely different polymer type. Poly(2-oxazoline)s (POx) constitute a versatile class of biocompatible synthetic polymers that uniquely enable access to numerous water-soluble macromolecules that can be rendered chiral, an attribute rarely accessible in synthetic stealth polymers. Here, we report the fabrication of crystalline-core nanorods bearing a chiral poly(2,4-dimethyl-2-oxazoline) (PdMeOx) corona via crystallisation-driven self-assembly (CDSA), and examine the influence of polymer chirality on biodistribution and antibody recognition in vivo. Well-defined enantiopure and racemic PdMeOx‑b‑poly(2‑(isopropyl)‑2‑oxazoline) block copolymers were synthesised and assembled into short nanorods with distinct optical activities, enabling a detailed investigation of chirality-dependent bio–nano interactions. We demonstrate that polymer chirality induces the generation of enantiomer-specific antibodies, an effect that has not previously been reported for synthetic macromolecular nanomaterials. These findings reveal stereochemistry as an orthogonal design parameter for modulating immune interactions and suggest a future strategy in which alternating polymer chirality, rather than changing polymer type, can be exploited to mitigate antibody-mediated clearance through structured dosing regimens.

Biobased, biodegradable, and biocompatible polymers provide a sustainable alternative to petrochemical-derived stabilisers, introducing green chemistries for advanced nanomedicine applications.

The stabilization of iron oxide nanoparticles (IONPs) with polymer coatings has received immense research interest as it improves their aqueous dispersion and enhances their pharmacokinetics and biodistribution. A range of functional groups including carboxylic acids, silanes, catechols , and phosphonic acids have been incorporated into polymers and investigated as anchoring groups for IONPs surfaces. While some anchors suffer from limitations such as low affinity, poor stability and undesirable reactivity with some substrate surfaces, pentavalent phosphonic acid groups have been shown to be one of the most effective. Here, a new and alternative polymer‐based stabilization strategy for IONPs in aqueous solution, using arsonic acid functional polymers PEG‐ b ‐P(AsAm)‐IONPs has been developed. The arsonic acid groups were shown to provide efficient and stable anchoring to the IONPs surface with transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirming particle colloidal stability in water and in phosphate‐buffered saline over extended periods of time. Importantly, these polymeric scaffolds are cytocompatible with mouse fibroblast cells (NIH/3T3), encouraging their future biomedical applications.