A nanomotor based strategy for fast cellular entry and cargo delivery is presented. The concept focuses on integrating tat peptide, a basic domain of HIV-1 tat protein, with state of the art nanomotors which possess attractive autonomous properties, facilitating cellular penetration and uptake. The rapid cellular internalization process leads to higher delivery efficiency.

Inspired by highly efficient natural motors, synthetic micro/nanomotors are self-propelled machines capable of converting the supplied fuel into mechanical motion. A significant advance has been made in the construction of diverse motors over the last decade. These synthetic motor systems, with rapid transporting and efficient cargo towing abilities, are expected to open up new horizons for various applications. Utilizing emergent motor platforms for in vivo applications is one important aspect receiving growing interest as conventional therapeutic methodology still remains limited for cancer, heart, or vasculature diseases. In this review we will highlight the recent efforts towards realistic in vivo application of various motor systems. With ever booming research enthusiasm in this field and increasing multidisciplinary cooperation, micro/nanomotors with integrated multifunctionality and selectivity are on their way to revolutionize clinical practice.

AbstractThe development of artificial nanomotor systems that are stimuli-responsive is still posing many challenges. Herein, we demonstrate the self-assembly of a redox-responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli-responsive nanomotors are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox-responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.

AbstractInspired by the self-migration of microorganisms in nature, artificial micro- and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. These self-propelled micro- and nanomotors, designed either by top-down or bottom-up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro-/nanosurgery. For these various applications, especially biomedical applications, regulating on-demand the motion of micro- and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro- and nanomotors by different approaches.

We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 μm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.Keywords: biodegradable; drug delivery; hybrid; nanomotors; self-assembly;

Fluidic channels were employed to induce the self-assembly of poly(ethylene glycol)-b-polystyrene into polymeric vesicles and nanotubes. The laminar flow in the device enables controlled diffusion of two miscible liquids at the phase boundary, leading to the formation of homogeneous polymeric structures of different shapes. These structures could be easily loaded with small molecule cargoes and functionalized with nanometer sized catalytic platinum nanoparticles. This technique offers a facile methodology to rapidly and continuously produce well-defined polymeric structures for nanotechnology applications.

Fluidic channels were employed to induce the self-assembly of poly(ethylene glycol)-b-polystyrene into polymeric vesicles and nanotubes. The laminar flow in the device enables controlled diffusion of two miscible liquids at the phase boundary, leading to the formation of homogeneous polymeric structures of different shapes. These structures could be easily loaded with small molecule cargoes and functionalized with nanometer sized catalytic platinum nanoparticles. This technique offers a facile methodology to rapidly and continuously produce well-defined polymeric structures for nanotechnology applications.

Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal “click” chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research.

We report a facile methodology for the formation of uniform small-sized poly(ethylene glycol)-block-polystyrene (PEG-b-PS) polymersomes, via extrusion and sonication methods by using organic solvent as plasticizing agent. The obtained polymersomes have diameters less than 100 nm. The size and size distribution depend on the organic solvent content and sonication time. The small-sized polymersomes are able to carry both hydrophobic and hydrophilic dyes.

Every living cell is a compartmentalized out-of-equilibrium system exquisitely able to convert chemical energy into function. In order to maintain homeostasis, the flux of metabolites is tightly controlled by regulatory enzymatic networks. A crucial prerequisite for the development of lifelike materials is the construction of synthetic systems with compartmentalized reaction networks that maintain out-of-equilibrium function. Here, we aim for autonomous movement as an example of the conversion of feedstock molecules into function. The flux of the conversion is regulated by a rationally designed enzymatic reaction network with multiple feedforward loops. By compartmentalizing the network into bowl-shaped nanocapsules the output of the network is harvested as kinetic energy. The entire system shows sustained and tunable microscopic motion resulting from the conversion of multiple external substrates. The successful compartmentalization of an out-of-equilibrium reaction network is a major first step in harnessing the design principles of life for construction of adaptive and internally regulated lifelike systems.

Self-powered artificial nanomotors are currently attracting increased interest as mimics of biological motors but also as potential components of nanomachinery, robotics, and sensing devices. We have recently described the controlled shape transformation of polymersomes into bowl-shaped stomatocytes and the assembly of platinum-driven nanomotors. However, the platinum encapsulation inside the structures was low; only 50% of the structures contained the catalyst and required both high fuel concentrations for the propelling of the nanomotors and harsh conditions for the shape transformation. Application of the nanomotors in a biological setting requires the nanomotors to be efficiently propelled by a naturally available energy source and at biological relevant concentrations. Here we report a strategy for enzyme entrapment and nanomotor assembly via controlled and reversible folding of polymersomes into stomatocytes under mild conditions, allowing the encapsulation of the proteins inside the stomach with almost 100% efficiency and retention of activity. The resulting enzyme-driven nanomotors are capable of propelling these structures at low fuel concentrations (hydrogen peroxide or glucose) via a one-enzyme or two-enzyme system. The confinement of the enzymes inside the stomach does not hinder their activity and in fact facilitates the transfer of the substrates, while protecting them from the deactivating influences of the media. This is particularly important for future applications of nanomotors in biological settings especially for systems where fast autonomous movement occurs at physiological concentrations of fuel.Keywords: autonomous movement; biofuel; nanomotor; stomatocytes; supramolecular chemistry;

•Polymersome shape is determined by a combination of QELS and MALS.•Asymmetric flow field flow fractionation is mandatory for effective analysis.•The ratio of Rg over Rh identifies spheres from prolates and oblates.•The measured values are in qualitative agreement with theory.Polymersomes, vesicles self-assembled from amphiphilic block copolymers, are well known for their robustness and for their broad applicability. Generating polymersomes of different shape is a topic of recent attention, specifically in the field of biomedical applications. To obtain information about their exact shape, tomography based on cryo-electron microscopy is usually the most preferred technique. Unfortunately, this technique is rather time consuming and expensive. Here we demonstrate an alternative analytical approach for the characterization of differently shaped polymersomes such as spheres, prolates and discs via the combination of multi-angle light scattering (MALS) and quasi-elastic light scattering (QELS). The use of these coupled techniques allowed for accurate determination of both the radius of gyration (Rg) and the hydrodynamic radius (Rh). This afforded us to determine the shape ratio ρ (Rg/Rh) with which we were able to distinguish between polymersome spheres, discs and rods.

Micro- and nano-motors are a class of miniaturized man-made machines that are able to convert chemical or external energy into mechanical motion. The past decade has witnessed significant progress in the design and fabrication of micro- and nano-motors as a future intelligent and comprehensive biomedical platform. In this review we will critically assess the challenges and limitations of micro- and nano-motors, their mechanism of propulsion and applications in the biomedical field. Important insights into the future development and direction of nano-motors for improved biocompatibility and design will be discussed.

Magnetic birefringence was used for in situ monitoring of the morphological changes in diamagnetic polymersomes during shape-transformation by dialysis. The birefringence was found to be very sensitive to the polymersome morphology, as determined by electron microscopy. The deflation of polymersomes into disks was observed, followed by a bending and partial inflation into stomatocytes.

The effect of the fuel concentration on the movement of self-assembled nanomotors based on polymersomes is reported. Positive control over the speed of the nanomotors and insights into the mechanism of propulsion are presented.

Polymersomes assembled from amphiphilic block copolymers containing a glassy hydrophobic segment can be further re-engineered to perform a controlled shape transformation from a thermodynamically stable spherical morphology to a kinetically trapped stomatocyte structure. The stable bowl-shape stomatocyte morphology is ideal for the specific physical entrapment of nanoparticles for potential use in heterogeneous catalysis and drug delivery. Herein we report two approaches to obtain a selective and controlled entrapment of platinum nanoparticles (PtNP) of different sizes and shapes inside the stomatocyte structure. In the first approach, the stomach of the stomatocytes is used to template the growth of the PtNP by controlling and confining the nucleation points inside the cavity. In the second method, preformed nanoparticles are engulfed during the stomatocyte formation process. Synergistically, the reverse effect is observed, that is, differently shaped nanoparticles were shown to exhibit a templating effect on the stomach formation of the stomatocytes.

A nanomotor based strategy for fast cellular entry and cargo delivery is presented. The concept focuses on integrating tat peptide, a basic domain of HIV-1 tat protein, with state of the art nanomotors which possess attractive autonomous properties, facilitating cellular penetration and uptake. The rapid cellular internalization process leads to higher delivery efficiency.

Micro- and nano-motors are a class of miniaturized man-made machines that are able to convert chemical or external energy into mechanical motion. The past decade has witnessed significant progress in the design and fabrication of micro- and nano-motors as a future intelligent and comprehensive biomedical platform. In this review we will critically assess the challenges and limitations of micro- and nano-motors, their mechanism of propulsion and applications in the biomedical field. Important insights into the future development and direction of nano-motors for improved biocompatibility and design will be discussed.

Magnetic birefringence was used for in situ monitoring of the morphological changes in diamagnetic polymersomes during shape-transformation by dialysis. The birefringence was found to be very sensitive to the polymersome morphology, as determined by electron microscopy. The deflation of polymersomes into disks was observed, followed by a bending and partial inflation into stomatocytes.