The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b -PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications.

Polymeric nano‐ and microscale materials bear significant potential in manifold applications related to biomedicine. This is owed not only to the large chemical diversity of the constituent polymers, but also to the various morphologies these materials can achieve, ranging from simple particles to intricate self‐assembled structures. Modern synthetic polymer chemistry permits the tuning of many physicochemical parameters affecting the behavior of polymeric nano‐ and microscale materials in the biological context. In this Perspective, an overview of the synthetic principles underlying the modern preparation of these materials is provided, aiming to demonstrate how advances in and ingenious implementations of polymer chemistry fuel a range of applications, both present and prospective.

The charge density of polymers involved in drug delivery is a key parameter during cellular uptake; moreover, the nature of charged groups determines the encapsulation efficiency and nanocarrier stability. Unfortunately, the high toxicity and the burst release of loaded cargo are their major drawbacks. We have developed here a versatile strategy to design photo-responsive nanocarriers showing high stability, slow-release properties and low cytotoxicity. These delivery vehicles are intended to prolong the drug effect, reducing the dose frequency, decreasing the side effects and maintaining a proper level of the drug. Diblock copolymers based on poly(dimethylsiloxane) and poly(2-dimethylaminoethyl methacrylate) containing pendant photo-cleavable 2-nitrobenzyl moieties were synthesized by atom transfer radical polymerization and post-polymerization modification, and then self-assembled into nanoparticles. Dynamic light scattering and transmission electron microscopy showed that the size and morphology of nanoparticles were not affected by UV exposure. Nanoparticle cytotoxicity was evaluated in relation to the number and nature of positively charged units. The nanocarriers containing copolymers with a longer charged block were successfully taken up by cells and were non-toxic both before and after irradiation up to 300 μg mL⁻¹. The slow photo-induced release of a negatively charged molecule, sulforhodamine B, reveals that the delivery is controlled not only by the photo-triggered transformation of hydrophilic blocks from cationic to zwitterionic, but also by a combination of forces that induce the self-assembly but do not allow the disruption of nanoparticles. Results suggest that this polymeric system plays a promising role as a nanocarrier for sustained, triggered drug delivery, preserving the non-toxicity after release.

Polymer assemblies on the nanoscale represent a powerful toolbox for the design of theranostic systems when combined with both therapeutic compounds and diagnostic reporting ones. Here, recent advances in the design of theranostic systems for various diseases, containing—in their architecture—either polymers or polymer assemblies as one of the building blocks are presented. This review encompasses the general principles of polymer self‐assembly, from the production of adequate copolymers up to supramolecular assemblies with theranostic functionality. Such polymer nanoassemblies can be further tailored through the incorporation of inorganic nanoparticles to endow them with multifunctional therapeutic and/or diagnostic features. Systems that change their architecture or properties in the presence of stimuli are selected, as responsivity to changes in the environment is a key factor for enhancing efficiency. Such theranostic systems are based on the intrinsic properties of copolymers or one of the other components. In addition, systems with a more complex architecture, such as multicompartments, are presented. Selected systems indicate the advantages of such theranostic approaches and provide a basis for further developments in the field.