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Introduction: Rapid excretion of drug derivatives often results in short drug half-lives, necessitating frequent administrations. Catalytic compartments, also known as nano- and microreactors, offer a solution by providing confined environments for in situ production of therapeutic agents. Inspired by natural compartments, polymer-based catalytic compartments have been developed to improve reaction efficiency and enable site-specific therapeutic applications., Areas Covered: Polymer-based compartments provide stability, permeability control, and responsiveness to stimuli, making them ideal for generating localized compounds/signals. These sophisticated systems, engineered to carry active compounds and enable selective molecular release, represent a significant advancement in pharmaceutical research. They mimic cellular functions, creating controlled catalytic environments for bio-relevant processes. This review explores the latest advancements in synthetic catalytic compartments, focusing on design approaches, building blocks, active molecules, and key bio-applications., Expert Opinion: Catalytic compartments hold transformative potential in precision medicine by improving therapeutic outcomes through precise, on-site production of therapeutic agents. While promising, challenges like scalable manufacturing, biodegradability, and regulatory hurdles must be addressed to realize their full potential. Addressing these will be crucial for their successful application in healthcare.

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.

Polymeric nanostructures obtained through self-assembly of reduction-sensitive amphiphilic triblock copolymers were investigated as potential drug delivery systems. The characteristic feature of these polymers is their cleavable disulfide bond in the center of the hydrophobic block. Therefore, the triblock copolymers can be cleaved into amphiphilic diblock copolymers. A poly(2-hydroxyethyl methacrylate)-b-poly(butyl methacrylate)-S-S-poly(butyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PHEMA-b-(PBMA-S-S-PBMA)-b-PHEMA) triblock copolymer was synthesized. It self-assembled into micelles which were used to encapsulate hydrophobic dye molecules (Nile Red, BodiPy 630/650) as model payloads. The self-assembled nanostructures disintegrated upon reduction of the disulfide bond, releasing their cargo and yielding larger particles that formed aggregates in solution after 24 h. A burst release of payload was shown within the first 15 min, followed by a constant release over several hours. As concentration gradients of reducing agents are commonly found in biological systems, the micelles could be used as redox-sensitive nanocarriers for the intracellular delivery of drugs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A promising approach for addressing a range of diseases lies in the delivery of functional biomacromolecules such as nucleic acids or proteins to cells. Polymers, peptides and the different shapes accessible through self-assembly of polymeric and peptidic amphiphiles have been widely explored as carriers and as containers for reactions on the nanoscale. These building blocks are particularly interesting, because several essential parameters such as physical characteristics, conditions for degradation or biocompatibility can be tuned to suit specific requirements. In this review, different three-dimensional architectures ranging from dendrimers and hyperbranched molecules to micelles, vesicles and nanoparticles assembled from synthetic polymers and peptides are discussed. It is focused on their function as a carrier for biologically active macromolecules, highlighting seminal examples from the current literature and pointing out the remaining and upcoming challenges in this important area of research.