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Polymersome nanoreactors that can be employed as artificial organelles have gained much interest over the past decades. Such systems often include biological catalysts (i.e., enzymes) so that they can undertake chemical reactions in cellulo. Examples of nanoreactor artificial organelles that acquire metal catalysts in their structure are limited, and their application in living cells remains fairly restricted. In part, this shortfall is due to difficulties associated with constructing systems that maintain their stability in vitro, let alone the toxicity they impose on cells. In this paper, we demonstrate a biodegradable and biocompatible polymersome nanoreactor platform, which can be applied as artificial organelle in living cells. We show the ability of our artificial organelles to, covalently and non-covalently, incorporate tris(triazolylmethyl)amine ligands complexing Cu(I) metal in their membrane. Such artificial organelles are capable of effectively catalyzing CuAAC reactions intracellularly, without compromising the cells' integrity. Our platform represents a step forward in the application of polymersome-based nanoreactors as artificial organelles. This article is protected by copyright. All rights reserved.

Synthetic nanomotors are appealing delivery vehicles for the dynamic transport of functional cargo. Their translation toward biological applications is limited owing to the use of non‐degradable components. Furthermore, size has been an impediment owing to the importance of achieving nanoscale (ca. 100 nm) dimensions, as opposed to microscale examples that are prevalent. Herein, we present a hybrid nanomotor that can be activated by near‐infrared (NIR)‐irradiation for the triggered delivery of internal cargo and facilitated transport of external agents to the cell. Utilizing biodegradable poly(ethylene glycol)‐b‐poly(d,l‐lactide) (PEG‐PDLLA) block copolymers, with the two blocks connected via a pH sensitive imine bond, we generate nanoscopic polymersomes that are then modified with a hemispherical gold nanocoat. This Janus morphology allows such hybrid polymersomes to undergoing photothermal motility in response to thermal gradients generated by plasmonic absorbance of NIR irradiation, with velocities ranging up to 6.2±1.10 μm s−1. These polymersome nanomotors (PNMs) are capable of traversing cellular membranes allowing intracellular delivery of molecular and macromolecular cargo., Delivery driver: Photo‐activated polymersome nanomotors (PNMs) composed of a biodegradable polymersome system coated with a hemisphere gold layer were utilized for intracellular delivery of molecular cargo via the assistance of a NIR laser. The active penetration of the cell membrane by the nanomotors allowed both encapsulated payloads and surrounding cargo to be delivered into cells.

A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo., Herein, hierarchical protocells are engineered by multistep, noncovalent assembly generating subcompartmentalized, membranized, coacervates—a functional model of eukaryotic spatial organization.

In this study a histidine containing elastin-like polypeptide (ELP) diblock copolymer is described with multiresponsive assembly behavior. Self-assembly into micelles is examined by two methods. First, the self-assembly is triggered by the addition of divalent metal ions, with Zn2+ being the most suitable one. Increasing the Zn2+ concentration stabilizes the nanoparticles over a large temperature window (4—45 °C). This diblock exhibits furthermore pH-responsiveness, and particles disassemble under mildly acidic conditions. Second, the coassembly of this ELP with a diblock ELP is examined, which is not responsive to pH and metal ions. Coassembly is triggered by heating the ELPs quickly above the transition temperature of the less hydrophobic block, which results in stable nanoparticles without the need to add metal ions. This novel ELP system offers a versatile modular nanocarrier platform that can respond to different stimuli and can be tuned effectively.

We report a near-infrared (NIR) light-powered Janus mesoporous silica nanomotor (JMSNM) with macrophage cell membrane (MPCM) cloaking that can actively seek cancer cells and thermomechanically percolate cell membrane. Upon exposure to NIR light, a heat gradient across the Janus boundary of the JMSNMs is generated by the photothermal effect of the Au half-shells, resulting in a self-thermophoretic force that propels the JMSNMs. In biological medium, the MPCM camouflaging can not only prevent dissociative biological blocks from adhering to JMSNMs but also improve the seeking sensitivity of the nanomotors by specifically recognizing cancer cells. The biofriendly propulsion and recognition capability enable JMSNMs to achieve the active seeking and bind to the membrane of cancer cells. Subsequent illumination with NIR then triggers the photothermal effect of MPCM@JMSNMs to thermomechanically perforate the cytomembranes for guest molecular injection. This approach integrates the functions of active seeking, cytomembranes perforating, and thermomechanical therapy in nanomotors, which may pave the way to apply self-propelled motors in biomedical fields.

We report the construction of erythrocyte membrane-cloaked Janus polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR) laser irradiation and are successfully applied in thrombus ablation. Chitosan (a natural polysaccharide with positive charge, CHI) and heparin (glycosaminoglycan with negative charge, Hep) were selected as wall materials to construct biodegradable and biocompatible capsules through the layer-by-layer self-assembly technique. By partially coating the capsule with a gold (Au) layer through sputter coating, a NIR-responsive Janus structure was obtained. Due to the asymmetric distribution of Au, a local thermal gradient was generated upon NIR irradiation, resulting in the movement of the JPMs through the self-thermophoresis effect. The reversible "on/off" motion of the JPMs and their motile behavior were easily tuned by the incident NIR laser intensity. After biointerfacing the Janus capsules with an erythrocyte membrane, the EM-JPMs displayed red blood cell related properties, which enabled them to move efficiently in relevant biological environments (cell culture, serum, and blood). Furthermore, this therapeutic platform exhibited excellent performance in ablation of thrombus through photothermal therapy. As man-made micromotors, these biohybrid EM-JPMs hold great promise of navigating in vivo for active delivery while overcoming the drawbacks of existing synthetic therapeutic platforms. We expect that this biohybrid motor has considerable potential to be widely used in the biomedical field.

The rapid emergence of nanotechnology and biotechnology provides revolutionary developments for drug delivery system. Recently, drug delivery has been attracted extensive research interest; great efforts have been contributed to improve the functions of these carriers and their applications. Active drug delivery is currently approved as an ideal approach for targeted transportation in the biological entity, and can cooperate with therapeutic mediums and transporting cargoes. In this review, several active targeted cargo mediated drug delivery patterns have been summarized including molecular motor, bio-camouflaged particles, and self-propelled nanomotors. Subsequently, a series of active targeted carriers for the drug delivery was introduced, and the possessions of targeted binding are discussed. Furthermore, the mechanism of active targeted transportation was exploited in detail; some of the promising works are highlighted.

Lipid bilayer membranes supported on polyelectrolyte multilayers are widely used as a new biomembrane model that connects biological and artificial materials since these ultrathin polyelectrolyte supports may mimic the role of the extracellular matrix and cell skeleton in living systems. Polyelectrolyte multilayers were fabricated by a layer-by-layer self-assembly technique. A quartz crystal microbalance with dissipation was used in real time to monitor the interaction between phospholipids and polyelectrolytes in situ on a planar substrate. The surface properties of polyelectrolyte films were investigated by the measurement of contact angles and zeta potential. Phospholipid charge, buffer pH and substrate hydrophilicity were proved to be essential for vesicle adsorption, rupture, fusion and formation of continuous lipid bilayers on the polyelectrolyte multilayers. The results clearly demonstrated that only the mixture of phosphatidylcholine and phosphatidic acid (4 : 1) resulted in fluid bilayers on chitosan and alginate multilayers with chitosan as a top layer at pH 6.5. A coarse-grained molecular simulation study elucidated that the exact mechanism of the formation of fluid lipid bilayers resembles a "parachute" model. As the closest model to the real membrane, polyelectrolyte multilayer-cushioned fluid lipid bilayers can be appropriate candidates for application in biomedical fields.

Photothermal therapies utilizing gold nanostructures are widely investigated and used within state-of-the-art noninvasive approaches. Single, isolated gold nanoparticles are unable to produce high enough temperatures to perform a sufficient wound closure, requiring therefore large amounts and concentrations to facilitate a therapeutic effect. In this proof of principle study we prepare composite micro-particles which contain near-infrared laser sensitive gold nanorods (GNRs) and Fe 3 O 4 superparamagnetic particles which are agglommerated in a layered polyelectrolyte multilayer (PEM) matrix. The GNRs-Fe 3 O 4 -PEM particles can be enriched in tissue incisions by applying a magnetic field. With this magnetic filed a targeted agglomeration is observed which is beneficial for near-infrared laser based wound sealing. Mechanical tests show that laser treated skin recovered closest to pristine samples and is comparable with nanoparicle gluing. The healing effect of this system is comparable with clinical sutures and nanoparticle gluing in in-vivo experiments. The observation that internal organs like liver can be welded with such composite particles opens new applications for laser tissue welding.

Macrophage cell membrane (MPCM)-camouflaged gold nanoshells (AuNS) that can serve as a new generation of photothermal conversion agents for in vivo photothermal cancer therapy are presented. They are constructed by the fusion of biocompatible AuNSs and MPCM vesicles. The resulting MPCM-coated AuNSs exhibited good colloidal stability and kept the original near-infrared (NIR) adsorption of AuNSs. Because AuNS carried high-density coverage of MPCMs, the totally functional portions of macrophage cells membrane were grafted onto the surface of AuNSs. This surface functionalization provided active targeting ability by recognizing tumor endothelium and thus improved tumoritropic accumulation compared to the red blood cell membrane-coating approach. These biomimetic nanoparticles significantly enhance in vivo blood circulation time and local accumulation at the tumor when administered systematically. Upon NIR laser irradiation, local heat generated by the MPCM-coated AuNS achieves high efficiency to suppress tumor growth and selectively ablate cancerous cells within the illuminated zone. Therefore, MPCM-coated AuNSs remained the natural properties of their source cells, which may improve the efficacy of photothermal therapy modulated by AuNSs and other noble-metal nanoparticles.

Surface engineering of synthetic carriers is an essential and important strategy for drug delivery in vivo. However, exogenous properties make synthetic nanosystems invaders that easily trigger the passive immune clearance mechanism, increasing the retention effect caused by the reticuloendothelial systems and bioadhesion, finally leading to low therapeutic efficacy and toxic effects. Recently, a cell membrane cloaking technique has been reported as a novel interfacing approach from the biological/immunological perspective, and has proved useful for improving the performance of synthetic nanocarriers in vivo. After cell membrane cloaking, nanoparticles not only acquire the physiochemical properties of natural cell membranes but also inherit unique biological functions due to the presence of membrane-anchored proteins, antigens, and immunological moieties. The derived biological properties and functions, such as immunosuppressive capability, long circulation time, and targeted recognition integrated in synthetic nanosystems, have enhanced their potential in biomedicine in the future. Here, we review the cell membrane-covered nanosystems, highlight their novelty, introduce relevant biomedical applications, and describe the future prospects for the use of this novel biomimetic system constructed from a combination of cell membranes and synthetic nanomaterials.

Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)‐block‐poly(D,L‐lactide), possess an oblate‐like morphology reminiscent of RBCs. This unique dual‐compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen‐binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano‐RBCs have long circulation times in mice, with the membrane‐coated ones outperforming the uncoated stomatoctyes. The capacity of nano‐RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer‐induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

We report a self-propelled Janus micromotor composed by chitosan (CHI) and alginate (ALG) multilayer capsule driven by near-infrared (NIR) illumination. The CHI/ALG multilayer capsules were prepared using conventional template-assisted layer-by-layer (LbL) self-assembly. Subsequently, gold nanorods (GNRs) were deposited on one side of the assembled capsules using microcontact printing method. The GNRs-modified Janus capsules can be driven by NIR irradiation owing to the generated thermal gradient and no additional chemical fuel are requested. It is also shown the moving speed of these Janus micromotors can be regulated by irradiation intensity and reach to 23.27 μm/s at a laser power of 9.6 J/cm2. Since no additional chemical component as fuel, this GNRs-modified ALG/CHI multilayer Janus capsule micromotor shows great potential as a biomimetic delivery platform in biomedical field.

Engineering natural macrophage cell membrane-camouflaged mesoporous silica nanocapsules can reduce the arrested percentage of immune cells and tissues, effectively prolong the survival time of nanoparticles in blood circulation system, and improve the accumulation in tumor.

Engineering self-propelled micromotors with good biocompatibility and biodegradability for actively seeking disease sites and targeted drug transport remains a huge challenge. In this study, neutrophils with intrinsic chemotaxis capability were transformed into self-guided hybrid micromotors by integrating mesoporous silica nanoparticles (MSNs) with high loading capability. To ensure the compatibility of neutrophil cells with drug-loaded MSNs, bacteria membranes derived from E. coli were coated on MSNs in advance by a camouflaging strategy. The resulting biohybrid micromotors inherited the characteristic chemotaxis capability of native neutrophils and could effectively move along the chemoattractant gradients produced by E. coli. Our studies suggest that this camouflaging approach, which favors the uptake of MSNs into neutrophils without loss of cellular activity and motility, could be used to construct synthetic nanoparticle-loaded biohybrid micromotors for advanced biomedical applications.

Bacterial infections, especially multidrug-resistant bacterial infections, are an increasingly serious problem in the field of wound healing. Herein, bacterial cellulose (BC) decorated by 4,6-diamino-2-pyrimidinethiol (DAPT)-modified gold nanoparticles (Au-DAPT NPs) is presented as a dressing (BC-Au-DAPT nanocomposites) for treating bacterially infected wounds. BC-Au-DAPT nanocomposites have better efficacy (measured in terms of reduced minimum inhibition concentration) than most of the antibiotics (cefazolin/sulfamethoxazole) against Gram-negative bacteria, while maintaining excellent physicochemical properties including water uptake capability, mechanical strain, and biocompatibility. On Escherichia coli- or Pseudomonas aeruginosa-infected full-thickness skin wounds on rats, the BC-Au-DAPT nanocomposites inhibit bacterial growth and promote wound repair. Thus, the BC-Au-DAPT nanocomposite system is a promising platform for treating superbug-infected wounds.

In this review, we summarize the recent progress made in the fabrication of pure natural materials such as biogenic capsules. Unlike polyelectrolyte capsules, biogenic capsules are primarily prepared with pure natural components using layer-by-layer (LbL) assembly on sacrificial templates. These capsules have been developed as smart materials for guest molecule encapsulation and delivery in the last two decades. With the extreme demands on biodegradability and biocompatibility, biogenic capsules exhibit unique properties that can be integrated with special ligands or conjugated functional groups for the design of intelligent platforms, significantly enriching their functions and applications.

We describe fuel-free, near-infrared (NIR)-driven Janus mesoporous silica nanoparticle motors (JMSNMs) with diameters of 50, 80, and 120 nm. The Janus structure of the JMSNMs is generated by vacuum sputtering of a 10 nm Au layer on one side of the MSNMs. Upon exposure to an NIR laser, a localized photothermal effect on the Au half-shells results in the formation of thermal gradients across the JMSNMs; thus, the generated self-thermophoresis can actively drive the nanomotors to move at an ultrafast speed, for instance, up to 950 body lengths/s for 50 nm JMSNMs under an NIR laser power of 70.3 W/cm(2). The reversible "on/off" motion of the JMSNMs and their directed movement along the light gradient can be conveniently modulated by a remote NIR laser. Moreover, dynamic light scattering measurements are performed to investigate the coexisting translational and rotational motion of the JMSNMs in the presence of both self-thermophoretic forces and strong Brownian forces. These NIR-powered nanomotors demonstrate a novel strategy for overcoming the necessity of chemical fuels and exhibit a significant improvement in the maneuverability of nanomotors while providing potential cargo transportation in a biofriendly manner.

Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.

Photothermal therapy based on gold nanostructures has been widely investigated as a state-of-the-art noninvasive therapy approach. Because single nanoparticles cannot harvest sufficient energy, self-assemblies of small plasmonic particles into large aggregates are required for enhanced photothermal performance. Self-assembled gold nanorods in lipid bilayer-modified microcapsules are shown to localize at tumor sites, generate vapor bubbles under near-infrared light exposure, and subsequently damage tumor tissues. The polyelectrolyte multilayer enables dense packing of gold nanorods during the assembly process, which leads to the formation of vapor bubbles around the excited capsules. The resulting vapor bubbles achieve a high efficiency of suppressing tumor growth compared to single gold nanorods. In vivo experiments demonstrated the ability of soft-polymer multilayer microcapsules to cross the biological barriers of the body and localize at target tissues.

We report a self-propelled Janus silica micromotor as a motion-based analytical method for achieving fast target separation of polyelectrolyte microcapsules, enriching different charged organics with low molecular weights in water. The self-propelled Janus silica micromotor catalytically decomposes a hydrogen peroxide fuel and moves along the direction of the catalyst face at a speed of 126.3 μm s(-1) . Biotin-functionalized Janus micromotors can specifically capture and rapidly transport streptavidin-modified polyelectrolyte multilayer capsules, which could effectively enrich and separate different charged organics in water. The interior of the polyelectrolyte multilayer microcapsules were filled with a strong charged polyelectrolyte, and thus a Donnan equilibrium is favorable between the inner solution within the capsules and the bulk solution to entrap oppositely charged organics in water. The integration of these self-propelled Janus silica micromotors and polyelectrolyte multilayer capsules into a lab-on-chip device that enables the separation and analysis of charged organics could be attractive for a diverse range of applications.

The synthesis of an innovative self-propelled Janus nanomotor with a diameter of about 75 nm that can be used as a drug carrier is described. The Janus nanomotor is based on mesoporous silica nanoparticles (MSNs) with chromium/platinum metallic caps and propelled by decomposing hydrogen peroxide to generate oxygen as a driving force with speeds up to 20.2 μm s(-1) (about 267 body lengths per second). The diffusion coefficient (D) of nanomotors with different H2 O2 concentrations is calculated by tracking the movement of individual particles recorded by means of a self-assembled fluorescence microscope and is significantly larger than free Brownian motion. The traction of a single Janus MSN nanomotor is estimated to be about 13.47×10(-15) N. Finally, intracellular localization and drug release in vitro shows that the amount of Janus MSN nanomotors entering the cells is more than MSNs with same culture time and particle concentrations, meanwhile anticancer drug doxorubicin hydrochloride loaded in Janus MSNs can be slowly released by biodegradation of lipid bilayers in cells.

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.

Biodegradable nanostructures displaying aggregation‐induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)‐block‐poly(caprolactone‐gradient‐trimethylene carbonate) (PEG‐P(CLgTMC)), with tetraphenylethylene pyridinium‐TMC (PAIE) side chains have been developed, which self‐assembled into well‐defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co‐encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy., Polymersomes with inherent aggregation‐induced emission are presented that have mitochondrial targeting capacity due to the presence of pyridinium groups. The AIEgenic polymersomes, upon encapsulation of photosensitizers, show efficient energy transfer to enable photodynamic therapy, which improves the therapeutic index against cancer cells both in vitro and in vivo.

Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.