Multifunctional and Dual-Responsive Polymersomes as Robust Nanocontainers: Design, Formation by Sequential Post-Conjugations, and pH-Controlled Drug Release

Robust, multiresponsive, and multifunctional nanovesicles are in high demand not only as carrier systems but also for applications in microsystem devices and nanotechnology. Hence, multifunctional, pH-responsive, and photo-cross-linked polymersomes decorated with adamantane and azide groups are prepared by mixed self-assembly of suitably end-modified block copolymers and are used for the subsequent postconjugation of the polymersome surface by using covalent and noncovalent approaches. For the covalent approach, nitroveratryloxycarbonyl-protected amine (NVOC) molecules as light-responsive moieties are introduced into the polymersomes through an azide–alkyne click reaction. After photocleavage of NVOC units, functional dye molecules react with the now freely accessible amine groups. The noncovalent approach is performed subsequently to introduce further moieties, making use of the strong adamantane-β-cyclodextrin host–guest interactions. It is quantitatively proven that all reactive groups have sufficient accessibility as well selective and orthogonal reactivity throughout these stepwise processes to allow the successful establishment of aimed pH- and light-responsive multifunctional polymersomes. Moreover, this sequential methodology is also applied to obtain doxorubicin-loaded multifunctional polymersomes for an efficient pH-controlled drug release. Overall, tunable membrane permeability combined with the potential for introducing multiple targeting groups by light-exposure or host–guest interactions make these smart polymersomes promising nanocontainers for many applications

Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase

Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane−β-cyclodextrin host–guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly­(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young’s modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors