Micro‐ and Nanocapsules: A Lively Field of Research

The confinement of bioactive molecules in well-defined capsules has been a topic of research which has met with growing interest in recent years. Many different types of capsules have been developed, which cover the dimensional range from the nano- to the micrometer size.1 The list of potential applications has steadily grown. In particular in the life sciences the utilization of these capsules has been shown to have much potential. Capsules can be used for the temporary storage of both small drugs and large biomolecules. They function as vehicles to protect and deliver their cargo to targeted tissues and cell types. Stimulus responsiveness can be built in to trigger release at the desired time and location. In other applications, capsules can be more regarded as nanoreactors, since the main task is to protect catalysts from undesired outside influences and to utilize the nanospace for more efficient turnover of substrates. The recent developments in this multidisciplinary research field at the interface of life sciences and materials justify this highly relevant and timely special issue in Macromolecular Bioscience. It is the purpose of this issue to show the broad spectrum of activities going on, from virus-based nanoreactors to micron-sized capsules prepared by microfluidics. Capsules can be constructed from bio(related) building blocks such as proteins, polypeptides and saccharides. One of the smallest types of capsules that can be formed is based on the protein mantle of plant viruses, such as the cowpea chlorotic mottle virus (CCMV). This mantle is composed of a range of identical capsid proteins, which are assembled via non-covalent interactions. For CCMV it has been demonstrated that for this assembly process the viral RNA is not required. This has allowed researchers to encapsulate in the core of the virus-like particle other molecules in place of the viral genetic material. Minten et al. have explored the use of non-covalent interactions based on leucine zippers to connect in an efficient way proteins to the inside surface of the nanocapsule.2 They have now systematically analyzed how this double non-covalent assembly process takes place.3 Another peptide-based vesicle is described by the Deming group. They have explored the usage of block copolypeptides for the construction of polymeric vesicles (polymersomes).4 Although these vesicles are already more stable than their low molecular weight analogues due to their macromolecular nature, it is for many applications useful to further increase stability. They now have shown that by using the recently reported DOPA crosslinking method, indeed greatly enhanced membrane stability is obtained.5 Upadhyay et al. have constructed block copolymers consisting of the hydrophobic poly(benzyl glutamate) and the hydrophilic polysaccharide hyaluronan, with which they formed polymersomes.6 The polymersomes were loaded with the anticancer drug docetaxel. With both in vitro and in vivo studies, they could show that this vehicle was highly efficient in enabling controlled drug release.7 Encapsulation of enzymes inside capsules protects them from undesired outside influences. If one wants to use these capsules not merely as storage devices, but also as nanoreactors, the polymeric shell should be permeable to a certain extent.8 Onaca et al. investigated the effect of polymer molecular weight on the efficiency of a polymersome-based nanoreactor containing the enzyme superoxide dismutase. In particular the length of the hydrophobic block determined the efficiency of the catalytic process.9 Traditionally, nanocapsules and nanoreactors are composed of a single compartment. For many processes however, the presence of more compartments within a capsule is desired, for example when substrate and enzyme have to be separated from each other until the moment that substrate conversion is required. Delcea et al. give an interesting overview of all the different methods that have recently been developed to construct multicompartment capsules, with application in both nanoreactors and drug delivery.10 There is a constant need for the development of new methodologies and capsule materials to improve on the existing capsules. Becker et al. have in this respect applied the DNA-analogous material peptide–nucleic acid (PNA).11 Using the layer-by-layer (LbL) method, stable PNA multilayers could be built up on a variety of scaffolds, including colloidal particles. After removal of the scaffold, capsules were obtained, which proved to be more stable against enzymatic degradation than their DNA counterparts. Degradation could be fine-tuned by using mixed DNA/PNA systems. The group of Rotello developed a microsphere consisting of a diamidopyridine functional scaffold, to which polymers with complementary thymine recognition units could be bound. When these assemblies were chemically crosslinked, a morphology change to vesicular structures was observed.12, 13 An important aspect of micro- and nanocapsules is their ability to harbor cargo and release it at the desired moment and place. Lensen et al. used microfluidics as a tool to construct well-defined polylactide micron-sized particles of which the core was composed of an organic solvent in which a hydrophobic model compound was dissolved.14 The organic solvent could be removed, which led to the formation of hollow capsules in which the model drug was adsorbed at the inside of the capsule shell. Lomas et al. further explored polymersomes as gene delivery systems composed of the DNA binding polymer poly(diisopropylamino methacrylate) and a hydrophilic polymethacrylate block with phosphorylcholine side chains.15 The interaction of the polymer with DNA was studied, as well as the encapsulation efficiency within the polymersome.16 Changing pH triggered disassembly and release of DNA. Another interesting method for release using external triggers is ultrasound. Pangu et al. showed that when polymersomes were treated for 10–20 min with an ultrasound source of 20 kHz, the polymersomes became leaky and released part of their content. When the ultrasound source was switched off, release stopped immediately. This process could be repeated several times, and fine tuned by changing for example the membrane thickness.17 This issue shows the versatility of capsule research. Creative capsule design is combined with exploration of new potential applications. As guest-editor of this issue, I am indebted to the leading scientists in the field that have enthusiastically contributed their latest research, making this issue exciting to read.