Stimuli‐responsive polymers have received increasing attention for various applications due to their ability to adapt physical and chemical properties in response to external environmental stimuli. In this regard, poly(N‐isopropylacrylamide) (PNIPAM) is the most extensively studied stimuli‐responsive polymer and, consequently has been prominently featured in (bio)‐sensor development, adaptive coating technology, drug delivery, wound healing, tissue regeneration, artificial actuator design, sensor technology, responsive coatings, and soft robotics. This success can be mainly attributed to the accessible and versatile nature of the PNIPAM platform, thus allowing the synthesis of a wide variety of copolymer architectures, topologies and compositions. Within this review, the structural and compositional features of PNIPAM‐based materials in sensor and biosensor applications are discussed with a focus on the literature from 2016 until now. The reader is provided with the current state of the art regarding PNIPAM‐based sensor development and their molecular design. Finally, the challenges ahead in the successful implementation of PNIPAM‐based sensors are highlighted, as well as the opportunities in the rational design of improved PNIPAM‐based sensors. Altogether, this review provides comprehensive insights into the exciting and rapidly expanding field of PNIPAM‐based sensing systems, which will benefit the chemical, pharmaceutical, textile, and biotech industries is believed.

Poly(2-alkyl/aryl-2-oxazoline)s (PAOx) are a class of cytocompatible polymers that have received growing interest over the past decade. This growing interest can mainly be attributed to their greater chemical versatility compared to other cytocompatible polymers, such as poly(ethylene glycol) (PEG), that originate from the diverse set of monomers compatible with the cationic ring-opening polymerization. Within this contribution we focus on the modification of methyl ester functional PAOx, on which we recently reported the quantitative conversion of methyl ester side chain bearing PAOx via direct amidation for a number of amines. While this approach is robust, it can be challenging to introduce certain amines, due to their high cost, poor solubility or additional functionalities. Here we evaluated three alternative amidation approaches of methyl ester side chain bearing PAOx with tyramine in terms of selectivity and quantitative conversion to the respective secondary amides. The amidation proceeded successfully via DMTMM coupling, PFP-activation and TBD catalysis, although only the latter 2 methods selectively yielded the desired product. In summary, we present valuable alternatives to our earlier reported method, contributing further to the biomedical application potential of PAOx.

Addressing the polymerization of 2-ethyl-2-oxazoline (EtOx) in ethyl acetate to replace the current state-of-the-art solvents. The switch to ethyl acetate is important towards pharmaceutical compliance/compatibility of PEtOx, besides low environmental burden.

Controlling the end‐groups of biocompatible polymers is crucial for enabling polymer‐based therapeutics and nanomedicine. Typically, end‐group diversification is a challenging and time‐consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end‐group diversification approach for poly(2‐oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation. The approach relies on the careful tuning of reaction parameters to establish differential reactivity of a pentafluorobenzyl initiator fragment and the living oxazolinium chain‐end, allowing the selective introduction of N‐, S‐, O‐nucleophiles via the termination of the polymerization, and a consecutive nucleophilic para‐fluoro substitution. The value of this approach for the accelerated development of nanomedicine is demonstrated through the synthesis of well‐defined lipid‐polymer conjugates and POx‐polypeptide block‐copolymers, which are well‐suited for drug and gene delivery. Furthermore, we investigated the application of a lipid‐POx conjugate for the formulation and delivery of mRNA‐loaded lipid nanoparticles for immunization against the SARS‐COV‐2 virus, underscoring the value of POx as a biocompatible polymer platform.