Synthetic micro/nanomotors have been extensively exploited over the past decade to achieve active transportation. This interest is a result of their broad range of potential applications, from environmental remediation to nanomedicine. Nevertheless, it still remains a challenge to build a fast-moving biodegradable polymeric nanomotor. Here we present a light-propelled nanomotor by introducing gold nanoparticles (Au NP) onto biodegradable bowl-shaped polymersomes (stomatocytes) via electrostatic and hydrogen bond interactions. These biodegradable nanomotors show controllable motion and remarkable velocities of up to 125 μm s⁻¹. This unique behavior is explained via a thorough three-dimensional characterization of the nanomotor, particularly the size and the spatial distribution of Au NP, with cryogenic transmission electron microscopy (cryo-TEM) and cryo-electron tomography (cryo-ET). Our in-depth quantitative 3D analysis reveals that the motile features of these nanomotors are caused by the nonuniform distribution of Au NPs on the outer surface of the stomatocyte along the z-axial direction. Their excellent motile features are exploited for active cargo delivery into living cells. This study provides a new approach to develop robust, biodegradable soft nanomotors with application potential in biomedicine.

Polymersomes that incorporate aggregation-induced emission (AIE) moieties are attractive inherently fluorescent nanoparticles with biomedical application potential for cell/tissue imaging and tracking, as well as phototherapeutics. An intriguing feature that has not been explored yet is their ability to adopt a range of asymmetric morphologies. Structural asymmetry allows nanoparticles to be exploited as active (motile) systems. Here, we present the design and preparation of AIE fluorophore integrated (AIEgenic) cucurbit-shaped polymersome nanomotors with enzyme-powered motility. The cucurbit scaffold was constructed via morphology engineering of biodegradable fluorescent AIE-polymersomes, followed by functionalization with enzymatic machinery via a layer-by-layer (LBL) self-assembly process. Because of the enzyme-mediated decomposition of chemical fuel on the cucurbit-like nanomotor surface, enhanced directed motion was attained, when compared with the spherical counterparts. These cucurbit-shaped biodegradable AIE-nanomotors provide a promising platform for the development of active delivery systems with potential for biomedical applications.

Functionalized polymer vesicles have been proven to be highly promising in biomedical applications due to their good biocompatibility, easy processability, and multifunctional responsive capacities. However, photothermal-responsive polymer vesicles triggered by near-infrared (NIR) light have not been widely reported until now. Herein, we propose a new strategy for designing NIR light-mediated photothermal polymer vesicles. A small molecule (PTA) with NIR-triggered photothermal features was synthesized by combining a D-D'-A-D'-D configuration framework with a molecular rotor function (TPE). The feasibility of the design strategy was demonstrated through density functional theory calculations. PTA moieties were introduced in the hydrophobic segment of a poly(ethylene glycol)-poly(trimethylene carbonate) block copolymer, of which the carbonate monomers were modified in the side chain with an active ester group. The amphiphilic block copolymers (PEG₄₄-PTA₂) were then used as building blocks for the self-assembly of photothermal-responsive polymer vesicles. The new class of functionalized polymer vesicles inherited the NIR-mediated high photothermal performance of the photothermal agent (PTA). After NIR laser irradiation for 10 min, the temperature of the PTA-Ps aqueous solution was raised to 56 °C. The photothermal properties and bilayer structure of PTA-Ps after laser irradiation were still intact, which demonstrated that they could be applied as a robust platform in photothermal therapy. Besides their photothermal performance, the loading capacity of PTA-Ps was investigated as well. Hydrophobic cargo (Cy7) and hydrophilic cargo (Sulfo-Cy5) were successfully encapsulated in the PTA-Ps. These properties make this new class of functionalized polymer vesicles an interesting platform for synergistic therapy in anticancer treatment.

Polymersome-based nanomotors represent a cutting-edge development in nanomedicine, merging the unique vesicular properties of polymersomes with the active propulsion capabilities of synthetic nanomotors. As a vesicular structure enclosed by a bilayer membrane, polymersomes can encapsulate both hydrophilic and hydrophobic cargoes. In addition, their physical–chemical properties such as size, morphology, and surface chemistry are highly tunable, which makes them ideal for various biomedical applications. The integration of motility into polymersomes enables them to actively navigate biological environments and overcome physiological barriers, offering significant advantages over passive delivery platforms. Recent breakthroughs in fabrication techniques and motion control strategies, including chemically, enzymatically, and externally driven propulsion, have expanded their potential for drug delivery, biosensing, and therapeutic interventions. Despite these advancements, key challenges remain in optimizing propulsion efficiency, biocompatibility, and in vivo stability to translate these systems into clinical applications. In this perspective, we discuss recent advancements in the preparation and motion control strategies of polymersome-based nanomotors, as well as their biomedical-related applications. The molecular design, fabrication approaches, and nanomedicine-related utilities of polymersome-based nanomotors are highlighted, to envisage the future research directions and further development of these systems into effective, precise, and smart nanomedicines capable of addressing critical biomedical challenges.

Polymersomes with surface-integrated nanoparticles, in which a smaller sphere is attached to a larger capsule, are typically formed through complex processes like membrane deformation, polymerization, or membrane functionalization. This complexity restricts facile application of this unusual topology, for example in drug delivery or nanomotor science. Our study introduces a robust method for crafting polymersomes with surface-integrated nanoparticles using a hierarchical phase separation approach. By co-assembling block copolymers with aromatic aggregation-induced emission (AIE) moieties as side chains and photothermal-responsive guest molecules (PTM), spontaneous sequential phase separation processes occur that lead to their controlled formation. Polymer-rich liquid droplets form first, followed by internal phase separation of the guest molecules, which determines the formation of asymmetric morphology. This mechanism is elucidated in detail using liquid-phase transmission and cryogenic transmission electron microscopy (LP-TEM and cryo-TEM) and corroborated by theoretical simulations of the interaction forces between the block copolymers and guest molecules. Finally, the application potential of polymersomes with surface-integrated nanoparticles as nanomotors is demonstrated.

Polymersomes, nanosized polymeric vesicles, have attracted significant interest in the areas of artificial cells and nanomedicine. Given their size, their visualization via confocal microscopy techniques is often achieved through the physical incorporation of fluorescent dyes, which however present challenges due to potential leaching. A promising alternative is the incorporation of molecules with aggregation-induced emission (AIE) behavior that are capable of fluorescing exclusively in their assembled state. Here, we report on the use of AIE polymersomes as artificial organelles, which are capable of undertaking enzymatic reactions in vitro. The ability of our polymersome-based artificial organelles to provide additional functionality to living cells was evaluated by encapsulating catalytic enzymes such as a combination of glucose oxidase/horseradish peroxidase (GOx/HRP) or β-galactosidase (β-gal). Via the additional incorporation of a pyridinium functionality, not only the cellular uptake is improved at low concentrations but also our platform's potential to specifically target mitochondria expands.