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The biological function of membranes is closely related to their softness, which is often studied through the membranes' thermally driven fluctuations. Typically, the analysis assumes that the relaxation rate of a pure bending deformation is determined by the competition between membrane bending rigidity and viscous dissipation in the surrounding medium. Here, we reexamine this assumption and demonstrate that viscous flows within the membrane dominate the dynamics of bending fluctuations of nonplanar membranes with a radius of curvature smaller than the Saffman-Delbrück length. Using flickering spectroscopy of giant vesicles made of dipalmitoylphosphatidylcholine, DPPC:cholesterol mixtures and pure diblockcopolymer membranes, we experimentally detect the signature of membrane dissipation in curvature fluctuations. We show that membrane viscosity can be reliably obtained from the short time behavior of the shape time correlations. The results indicate that the DPPC:cholesterol membranes behave as a Newtonian fluid, while the polymer membranes exhibit more complex rheology. Our study provides physical insights into the time scales of curvature remodeling of biological and synthetic membranes. [ABSTRACT FROM AUTHOR]

The ability to precisely control in vitro enzymatic reactions in synthetic cells plays a crucial role in the bottom‐up design of artificial cell models that can recapitulate the key cellular features and functions such as metabolism. However, integration of enzymatic reactions has been limited to bulk or microfluidic emulsions without a membrane, lacking the ability to design more sophisticated higher‐order artificial cell communities for reconstituting spatiotemporal biological information at multiple length scales. Herein, droplet microfluidics is utilized to synthesize artificial cell‐like polymersomes with distinct molecular permeability for spatiotemporal control of enzymatic reactions driven by external signals and fuels. The presence of a competing reverse enzymatic reaction that depletes the active substrates is shown to enable demonstration of fuel‐driven formation of sub‐microcompartments within polymersomes as well as realization of out‐of‐equilibrium systems. In addition, the different permeability characteristics of polymersome membranes are exploited to successfully construct a programmable enzymatic reaction network that mimics cellular communication within a heterogeneous cell community through selective molecular transport. [ABSTRACT FROM AUTHOR]

Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide–alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies. [ABSTRACT FROM AUTHOR]

Coarse-grained molecular dynamics simulations are employed to investigate the spatiotemporal evolution of vesicles (polymersomes) through the self-assembly of randomly distributed amphiphilic BAB triblock copolymers with hydrophilic A and hydrophobic B blocks in an aqueous solution. The vesiculation pathway consists of several intermediate structures, such as an interconnected network of copolymer aggregates, a cage of cylindrical micelles, and a lamellar cage. The cage-to-vesicle transition occurs at a constant aggregation number and practically eliminates the hydrophobic interfacial area between the B block and solvent. Molecular reorganization underlying the sequence of morphology transitions from a cage-like aggregate to a vesicle is nearly isentropic. The end-to-end distances of isolated copolymer chains in solution and those within a vesicular assembly follow lognormal probability distributions. This can be attributed to the preponderance of folded chain configurations in which the two hydrophobic end groups of a given chain stay close to each other. However, the probability distribution of end-to-end distances is broader for chains within the vesicle as compared with that of a single chain. This is due to the swelling of the folded configurations within the hydrophobic bilayer. Increasing the hydrophobicity of the B block reduces the vesiculation time without qualitatively altering the self-assembly pathway. [ABSTRACT FROM AUTHOR]

Coarse-grained molecular dynamic simulations are employed to investigate the spatiotemporal evolution of vesicles (polymersomes) via self-assembly of randomly distributed amphiphilic diblock copolymers PB-PEO (Poly(Butadiene)-b-Poly(Ethylene Oxide)) in water. The vesiculation pathway consists of several intermediate structures, such as spherical/rodlike aggregates, wormlike micelles, lamellae, and cavities. The lamella-to-vesicle transition occurs at a constant aggregation number and is accompanied by a reduction in the solvent-accessible surface area. Simulation predictions are in qualitative agreement with the mechanism of vesicle formation in which the unfavorable hydrophobic interactions between water molecules and polymer segments, along the edge of the lamella, are eliminated at the expense of gaining curvature energy. However, rod–lamella–vesicle transition is accompanied by an increase in copolymer packing density. Hence, the change in the surface area accompanying vesiculation predicted by the simulations is significantly lower than theoretical estimates. Changes in information entropy, quantified by the expectation of the logarithm of the probability distribution function of the segmental stretch parameter s, defined as the difference between the maximum and instantaneous segmental extension, are statistically insignificant along the vesiculation pathway. For rods, lamellae, and polymersomes, s follows a log normal distribution. This is explained based on the configurational dynamics of a single diblock chain in water. [ABSTRACT FROM AUTHOR]

Artificial cell and organelle construction has recently gained substantial attention to generate simplified models for understanding of biological phenomena, or micro‐ and nanomachines for biomedical and biotechnological applications. A wide array of building blocks has been employed to build these systems as membraneless structures with the ability to compartmentalize chemical reactions by enhanced partitioning, or as membrane‐defined entities that provide a physical barrier that inhibits the interference of external factors. While these systems present unique properties that enable high fidelity to biological processes, they present limited ability to recreate the high selectivity and specificity of small molecule trafficking observed in biological membranes. Owing to their high chemical versatility, polymers can be leveraged to generate 3D structures that resemble biological membranes while providing transmembrane chemical motifs that enable responsiveness to a wide array of stimuli. This Concept Article discusses the ability to control membrane transport facilitating the emergence of out‐of‐equilibrium feedback mechanisms that ultimately modulate enzymatic rates. This can be employed to engineer future artificial cells and organelles that display homeostasis as a mechanism of self‐adaptation to continuously evolving environments. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) therapies have emerged as potent and personalized alternatives to conventional DNA-based therapies. However, their therapeutic potential is frequently constrained by their molecular instability, susceptibility to degradation, and inefficient cellular delivery. This study presents the nanoparticle "ChargeSome" as a novel solution. ChargeSomes are designed to protect mRNAs from degradation by ribonucleases (RNases) and enable cell uptake, allowing mRNAs to reach the cytoplasm for protein expression via endosome escape. We evaluated the physicochemical properties of ChargeSomes using 1H nuclear magnetic resonance, Fourier-transform infrared, and dynamic light scattering. ChargeSomes formulated with a 9:1 ratio of mPEG-b-PLL to mPEG-b-PLL-SA demonstrated superior cell uptake and mRNA delivery efficiency. These ChargeSomes demonstrated minimal cytotoxicity in various in vitro structures, suggesting their potential safety for therapeutic applications. Inherent pH sensitivity enables precise mRNA release in acidic environments and structurally protects the encapsulated mRNA from external threats. Their design led to endosome rupture and efficient mRNA release into the cytoplasm by the proton sponge effect in acidic endosome environments. In conclusion, ChargeSomes have the potential to serve as effective secure mRNA delivery systems. Their combination of stability, protection, and delivery efficiency makes them promising tools for the advancement of mRNA-based therapeutics and vaccines. [ABSTRACT FROM AUTHOR]

The design of stimuli- responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS- b- PMOXA diblock copolymer to create a responsive self- assembled system. The successful incorporation and selective activation by low- power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)- approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems. [ABSTRACT FROM AUTHOR]

Coarse-grained molecular dynamics simulations that incorporate explicit water-mediated hydrophilic/hydrophobic interactions are employed to track spatiotemporal evolution of diblock copolymer aggregation in initially homogeneous solutions. A phase portrait of the observed morphologies and their quantitative geometric features such as aggregation numbers, packing parameters, and radial distribution functions of solvent/monomers are presented. Energetic and entropic measures relevant to self-assembly such as specific solvent accessible surface area (SASA) and probability distribution functions (pdfs) of segmental stretch of copolymer chains are analyzed. The simulations qualitatively capture experimentally observed morphological diversity in diblock copolymer solutions. Topologically simpler structures predicted include spherical micelles, vesicles (polymersomes), lamellae (bilayers), linear wormlike micelles, and tori. More complex morphologies observed for larger chain lengths and nearly symmetric copolymer compositions include branched wormlike micelles with Y-shaped junctions and cylindrical micelle networks. For larger concentrations, vesicle strands, held together by hydrogen bonds, and "giant" composite aggregates that consist of lamellar, mixed hydrophobic/hydrophilic regions and percolating water cores are predicted. All structures are dynamic and exhibit diffuse domain boundaries. Morphology transitions across topologically simpler structures can be rationalized based on specific SASA measurements. PDFs of segmental stretch within vesicular assemblies appear to follow a log-normal distribution conducive for maximizing configuration entropy. [ABSTRACT FROM AUTHOR]

Drugs with different solubility can be selectively embedded into polymersomes with the hydrophilic core and hydrophobic bilayer. Novel folate-targeted Pluronic/poly (D,L-lactide- b -glycolide) polymersomes were constructed and used for the co-delivery of paclitaxel (PTX) and doxorubicin (DOX) to improve their inhibitory effect over cancer cells. The particle size of blank polymersomes was mainly distributed below 125 nm. The release of PTX and DOX from polymersomes showed an initial burst release followed by a sustained and slow release. The in vitro cytotoxicity data showed that the targeted co-loaded polymersomes (PTX&DOX FA-Ps) exhibited better inhibitory effect than single-loaded polymersomes and free drugs did. Furthermore, PTX&DOX FA-Ps showed the synergistic therapeutic effect over OVCAR-3 cancer cells. The cellular uptake results also showed that folate modified polymersomes had excellent targeting performance. Therefore, the folate-targeted Pluronic/poly (D,L-lactide- b -glycolide) polymersomes have potential application value as novel drug carriers to co-deliver PTX and DOX. [ABSTRACT FROM AUTHOR]

Advances in atom transfer radical polymerization (ATRP) have enabled the precise design and preparation of nanostructured polymeric materials for a variety of biomedical applications. This paper briefly summarizes recent developments in the synthesis of bio-therapeutics for drug delivery based on linear and branched block copolymers and bioconjugates using ATRP, which have been tested in drug delivery systems (DDSs) over the past decade. An important trend is the rapid development of a number of smart DDSs that can release bioactive materials in response to certain external stimuli, either physical (e.g., light, ultrasound, or temperature) or chemical factors (e.g., changes in pH values and/or environmental redox potential). The use of ATRPs in the synthesis of polymeric bioconjugates containing drugs, proteins, and nucleic acids, as well as systems applied in combination therapies, has also received considerable attention. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways. [ABSTRACT FROM AUTHOR]

Membrane proteins (MPs) play key roles in cellular signaling pathways and are responsible for intercellular and intracellular interactions. Dysfunctional MPs are directly related to the pathogenesis of various diseases, and they have been exploited as one of the most sought-after targets in the pharmaceutical industry. However, working with MPs is difficult given that their amphiphilic nature requires protection from biological membrane or membrane mimetics. Polymersomes are bilayered nanovesicles made of self-assembled block copolymers that have been widely used as cell membrane mimetics for MP reconstitution and in engineering of artificial cells. This review highlights the prevailing trend in the application of polymersomes in MP study and drug discovery. We begin with a review on the techniques for synthesis and characterization of polymersomes as well as methods of MP insertion to form proteopolymersomes. Next, we review the structural and functional analysis of the different types of MPs reconstituted in polymersomes, including membrane transport proteins, MP complexes, and membrane receptors. We then summarize the factors affecting reconstitution efficiency and the quality of reconstituted MPs for structural and functional studies. Additionally, we discuss the potential in using proteopolymersomes as platforms for high-throughput screening (HTS) in drug discovery to identify modulators of MPs. We conclude by providing future perspectives and recommendations on advancing the study of MPs and drug development using proteopolymersomes. [ABSTRACT FROM AUTHOR]

Polymersomes possess the self-assembly vesicular structure similar to liposomes. Although a variety of comparisons between polymersomes and liposomes in the aspects of physical properties, preparation and applications have been elaborated in many studies, few focus on their differences in drug encapsulation, delivery and release in vitro and in vivo. In the present work, we have provided a modified direct hydration method to encapsulate anti-cancer drug paclitaxel (PTX) into PEG-b-PCL constituted polymersomes (PTX@PS). In addition to advantages including narrow particle size distribution, high colloid stability and moderate drug-loading efficiency, we find that the loaded drug aggregate in small clusters and reside through the polymersome membrane, representing a unique core-satellite structure which might facilitate the sustained drug release. Compared with commercial liposomal PTX formulation (Lipusu®), PTX@PS exhibited superb tumor cell killing ability underlain by multiple pro-apoptotic mechanisms. Moreover, endocytic process of PTX@PS significantly inhibits drug transporter P-gp expression which could be largely activated by free drug diffusion. In glioma mice models, it has also confirmed that PTX@PS remarkably eradicate tumors, which renders polymersomes as a promising alternative to liposomes as drug carriers in clinic. [ABSTRACT FROM AUTHOR]

Programmed release of small molecular drugs from polymersomes is of great importance in drug delivery. A significant challenge is to adjust the membrane permeability in a well-controlled manner. Herein, we propose a strategy for controlling membrane phase separation by photo-cross-linking of the membrane-forming blocks with different molecular architectures. We synthesized three amphiphilic block copolymers with different membrane-forming blocks, which are poly(ethylene oxide)43-b-poly((ε-caprolactone)45-stat-((a-(cinnamoyloxymethyl)-1,2,3-triazol)caprolactone)25) (PEO43-b-P(CL45-stat-CTCL25)), PEO43-b-P(CL108-stat-CTCL16), and PEO43-b-PCTCL4-b-PCL79. These polymers were self-assembled into polymersomes using either a solvent-switch or powder rehydration method, and the obtained polymersomes were characterized by dynamic light scattering and transmission electron microscopy. Then the phase separation patterns within the polymersome membranes were investigated by mesoscopic dynamics (MesoDyn) simulations. To further confirm the change of the membrane permeability that resulted from the phase separation within the membrane, doxorubicin, as a small molecular drug, was loaded and released from the polymersomes. Due to the incompatibility between membrane-forming moieties (PCTCL and PCL), phase separation occurs and the release rate can be tuned by controlling the membrane phase pattern or by photo-cross-linking. Moreover, besides the compacting effect by formation of chemical bonds in the membrane, the cross-linking process can act as a driving force to facilitate the rearrangement and re-orientation of the phase pattern, which also influences the drug release behavior by modulating the cross-membrane distribution of the amorphous PCTCL moieties. In this way, the strategy of focusing on the membrane phase separation for the preparation of the polymersomes with finely tunable drug release rate can be envisioned and designed accordingly, which is of great significance in the field of delivery vehicles for programmed drug release. [ABSTRACT FROM AUTHOR]

Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG–PDH–mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120–190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells. [ABSTRACT FROM AUTHOR]

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material's toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL10-b-PDMS65-b-PVCL10 vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg−1 single dose) of PVCL10-PDMS65-PVCL10 vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research. [ABSTRACT FROM AUTHOR]

The immunosuppressive tumor microenvironment (ITM) and low immunogenicity of tumors greatly limit cancer immunotherapy efficacy. The approach of solely depleting regulatory T cells (Tregs) cannot ameliorate ITM, but possibly worsen it since the produced apoptotic Tregs will activate the A2A signaling pathway and cause more severe immune suppression. To address it, in this work a pH-responsive polymersome (CY/ZM@CS-BPA) based on chondroitin sulfate (CS)-poly(β-amino ester) is rationally developed. In the acidic tumor microenvironment, the tertiary amine groups in the polymersome will reverse from hydrophobic to hydrophilic due to protonation, which leads to the disintegration of nanostructures and the release of cyclophosphamide (CY) and A2A receptor (A2AR) antagonist ZM241385 (ZM). CY can selectively deplete Tregs. Additionally, CY can induce immunogenic cell death (ICD) of tumor cells, which results in the proapoptotic translocation of calreticulin to the cell surface, further initiating the antitumor immune responses. ZM can inhibit the activation of the adenosine A2A pathway, subsequently preventing the differentiation of CD4+ T cells into Tregs and enhancing the cytotoxicity of CD8+ T cells. As a result, the combination of depleting regulatory T cells and blocking the A2A receptor can enhance cancer immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

Amphiphilic diblock copolymers may assemble in aqueous solutions to form vesicles delimited by a polymeric double layer, also known as polymersomes, considered a more robust option to liposomes. Diblock copolymers may respond to pH, temperature, and other conditions. Because of such properties, polymersomes are currently being studied as drug delivery systems or as nanoreactors. pH-responsive polymersomes are potentially crucial because unusual pH gradients are present in cells under several physiological and pathological conditions. We synthesized two diblock copolymers of poly [2-(dimethylamino) ethyl methacrylate]-block-polystyrene (PDMAEMA-b-PS) via RAFT. We both developed new materials and better-understood polymersomes' properties with pH and temperature-responsive groups with these polymers. GPC, 1H-NMR, and FTIR characterized copolymers. The ionization equilibrium of the PDMAEMA amino groups on the polymersomes was analyzed by potentiometric titration and Zeta potential measurements. The hydrodynamic radius of the polymersomes in different pH and temperatures was analyzed by DLS. Entrapment of an electron paramagnetic resonance probe indicated the presence of a hydrophilic inner core. Negative staining transmission electron microscopy showed spherical aggregates and confirmed the diameter around 80 nm. These polymersomes with dual stimulus–response (i.e., pH and temperature) may be a platform for gene delivery and nanoreactors. [ABSTRACT FROM AUTHOR]

A solvent annealing-induced structural reengineering approach is exploited to fabricate polymersomes from block copolymers that are hard to form vesicles through the traditional solution self-assembly route. More specifically, polystyrene-b-poly(4-vinyl pyridine) (PS-b-P4VP) particles with sphere-within-sphere structure (SS particles) are prepared by three-dimensional (3D) soft-confined assembly through emulsion-solvent evaporation, followed by 3D soft-confined solvent annealing upon the SS particles in aqueous dispersions for structural engineering. A water-miscible solvent (e.g., THF) is employed for annealing, which results in dramatic transitions of the assemblies, e.g., from SS particles to polymersomes. This approach works for PS-b-P4VP in a wide range of block ratios. Moreover, this method enables effective encapsulation/loading of cargoes such as fluorescent dyes and metal nanoparticles, which offers a new route to prepare polymersomes that could be applied for cargo release, diagnostic imaging, and nanoreactor, etc. [ABSTRACT FROM AUTHOR]

The clinical application of some natural molecules in therapy is usually limited due to the lack of feasible delivery systems. Core–shell nanocarriers (polymersomes and niosomes) are interesting stable nanocarriers that are biocompatible, biodegradable, and able to produce sustainable delivery. They can be modified and functionalized according to the application needed. In this report, we describe the synthesis of a smart and pH-responsive poly(ethylene oxide)-poly(lactide) polymersome (PEO-PL) and niosomes (NIO) loaded with GSH for efficient peptide delivery and potent application against advanced glycation end-products-related damages and toxicities. PEO-PL was constructed using the one-pot sequential anionic ring-opening polymerization method, while the niosomes were prepared via the thin film layer technique. The nanocarriers were characterized for their size and morphology by DLS and SEM. The formulations demonstrated a high encapsulation rate reaching 95% and showed increased sensitivity to release their content in acidic conditions (pH 5.5) compared with physiological media. PEO-PL showed a higher retention rate compared with the NIO. The nanocarriers showed no apparent toxicity even at high concentrations (400 µg/mL). The MTT test demonstrated that HeLa cell lines were more sensitive to GSH than U87 cell lines starting from 100 and 400 µg/mL, respectively. Testing the synthesized core–shell nanocarriers on altered proteins showed prolonged and high prevention rates of glycation, aggregation, and oxidation without hindering the effect of GSH. These bioresponsive nanocarriers appear as an interesting platform for biomedicine and therapy. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids are one of the many substances of abuse widely spreading in modern society. Medical practitioners and law enforcement alike highly seek portable, efficient, and reliable tools for on-site detection and diagnostics. Here, we propose a colorimetric lateral flow assay (LFA) combined with dye-loaded polymersome to detect the synthetic cannabinoid JWH-073 efficiently. Rhodamine B–loaded polymersome was conjugated to antibodies and fully characterized. Two LFA were proposed (sandwich and competitive), showing a high level of sensitivity with a limit of detection (LOD) reaching 0.53 and 0.31 ng/mL, respectively. The competitive assay was further analyzed by fluorescence, where the LOD reached 0.16 ng/mL. The application of the LFA over spiked synthetic saliva or real human saliva demonstrated an overall response of 94% for the sandwich assay and 97% for the competitive LFA. The selectivity of the system was assessed in the presence of various interferents. The analytical performance of the LFA system showed a coefficient of variation below 6%. The current LFA system appears as a plausible system for non-invasive detection of substance abuse and shows promise for synthetic cannabinoid on-site sensing. [ABSTRACT FROM AUTHOR]

In this study, a chemotherapeutic drug, Docetaxel (DTX) was loaded in a di‐block polymeric nanoparticles (NPs) consisted of Oleate and Poly (ethylene glycol). First, the OA‐PEG1000 units were synthesized by the esterification reaction and confirmed by 1HNMR and FTIR spectroscopies. After determination of critical micelle concentration (CMC), the DTX was loaded into the OA‐PEG1000 NPs using the solvent displacement method. The encapsulation efficiency and loading capacity percentages were estimated as 22.2 % and 0.43 % respectively. The average size (obtained by DLS) and zeta potential of NPs were as 221.3±8.06 nm and 6.31±0.29 mV respectively indicating polymersome formation. The morphology of NPs in AFM images was almost spherical with a diameter of about 207.1±28.36 nm which was approximate to DLS outcomes. These results demonstrated that di‐block polymeric NPs can be potentially practical for carrying and delivering DTX as a novel anticancer pharmaceutical. [ABSTRACT FROM AUTHOR]

Cytochrome bo3 ubiquinol oxidase is a transmembrane protein, which oxidizes ubiquinone and reduces oxygen, while pumping protons. Apart from its combination with F1Fo-ATPase to assemble a minimal ATP regeneration module, the utility of the proton pump can be extended to other applications in the context of synthetic cells such as transport, signaling, and control of enzymatic reactions. In parallel, polymers have been speculated to be phospholipid mimics with respect to their ability to self-assemble in compartments with increased stability. However, their usability as interfaces for complex membrane proteins has remained questionable. In the present work, we optimized a fusion/electroformation approach to reconstitute bo3 oxidase in giant unilamellar vesicles made of PDMS-g-PEO and/or phosphatidylcholine (PC). This enabled optical access, while microfluidic trapping allowed for online analysis of individual vesicles. The tight polymer membranes and the inward oriented enzyme caused 1 pH unit difference in 30 min, with an initial rate of 0.35 pH·min-1. To understand the interplay in these composite systems, we studied the relevant mechanical and rheological membrane properties. Remarkably, the proton permeability of polymer/lipid hybrids decreased after protein insertion, while the latter also led to a 20% increase of the polymer diffusion coefficient in polymersomes. In addition, PDMSg- PEO increased the activity lifetime and the resistance to free radicals. These advantageous properties may open diverse applications, ranging from cell-free biotechnology to biomedicine. Furthermore, the presented study serves as a comprehensive road map for studying the interactions between membrane proteins and synthetic membranes, which will be fundamental for the successful engineering of such hybrid systems. [ABSTRACT FROM AUTHOR]

Organelle-specific nanocarriers (NCs) are highly sought after for delivering therapeutic agents into the cell nucleus. This necessitates nucleocytoplasmic transport (NCT) to bypass nuclear pore complexes (NPCs). However, little is known as to how comparably large NCs infiltrate this vital intracellular barrier to enter the nuclear interior. Here, we developed nuclear localization signal (NLS)-conjugated polymersome nanocarriers (NLS-NCs) and studied the NCT mechanism underlying their selective nuclear uptake. Detailed chemical, biophysical, and cellular analyses show that karyopherin receptors are required to authenticate, bind, and escort NLS-NCs through NPCs while Ran guanosine triphosphate (RanGTP) promotes their release from NPCs into the nuclear interior. Ultrastructural analysis by regressive staining transmission electron microscopy further resolves the NLS-NCs on transit in NPCs and inside the nucleus. By elucidating their ability to utilize NCT, these findings demonstrate the efficacy of polymersomes to deliver encapsulated payloads directly into cell nuclei. [ABSTRACT FROM AUTHOR]

Extended-release local anesthetics (LAs) have drawn increasing attention with their promising role in improving analgesia and reducing adverse events of LAs. Nano-structured carriers such as liposomes and polymersomes optimally meet the demands of/for extended-release, and have been utilized in drug delivery over decades and showed satisfactory results with extended-release. Based on mature technology of liposomes, EXPAREL, the first approved liposomal LA loaded with bupivacaine, has seen its success in an extended-release form. At the same time, polymersomes has advances over liposomes with complementary profiles, which inspires the emergence of hybrid carriers. This article summarized the recent research successes on nano-structured extended-release LAs, of which liposomal and polymeric are mainstream systems. Furthermore, with continual optimization, drug delivery systems carry properties beyond simple transportation, such as specificity and responsiveness. In the near future, we may achieve targeted delivery and controlled-release properties to satisfy various analgesic requirements. [ABSTRACT FROM AUTHOR]

In recent years various polymeric vesicles have been reported that show promising results for drug delivery applications, nanomotors and/or nanoreactors. These polymeric vesicles can be assembled from many different materials and various coupling reactions have been applied for functionalization of the vesicles. However, the designs reported are still rather simple, as it is challenging to mimic biological complex systems. In this review we focus on the properties of widely used hydrophobic polymers to better understand polymersome properties for various applications. Examples are shown of how researchers have used and modulated block‐copolymers and their properties to their advantage. Furthermore, an overview of possible end group functionalizations of nanoparticles is reported, giving insight in recent developments of smart nanoparticles for biomedical applications. [ABSTRACT FROM AUTHOR]

Fluorescent polymersomes with both aggregation‐induced emission (AIE) and CO2‐responsive properties were developed from amphiphilic block copolymer PEG‐b‐P(DEAEMA‐co‐TPEMA) in which the hydrophobic block was a copolymer made of tetraphenylethene functionalized methacrylate (TPEMA) and 2‐(diethylamino)ethyl methacrylate (DEAEMA) with unspecified sequence arrangement. Four block copolymers with different DEAEMA/TPEMA and hydrophilic/hydrophobic ratios were synthesized, and bright AIE polymersomes were prepared by nanoprecipitation in THF/water and dioxane/water systems. Polymersomes of PEG45‐b‐P(DEAEMA36‐co‐TPEMA6) were chosen to study the CO2‐responsive property. Upon CO2 bubbling vesicles transformed to small spherical micelles, and upon Ar bubbling micelles returned to vesicles with the presence of a few intermediate morphologies. These polymersomes might have promising applications as sensors, nanoreactors, or controlled release systems. [ABSTRACT FROM AUTHOR]

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Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles (polymersomes) have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS) polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/(kg·week). Following the administration of a more relevant 20 mg/(kg·week) dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and > 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bl-PPS polymersomes into the clinic for therapeutic applications in humans. [ABSTRACT FROM AUTHOR]

Although gas-filled microbubbles with high echogenicity are widely applied inclinical ultrasonography, the micron scale particle size impedes their use in the treatment of solid tumors,which are accessible to objects less than several hundred nanometers. We herein propose an unusual approach involving apH-induced core-shell micelle-to-vesicle transition to prepare ultrasound-sensitive polymeric nanospheres (polymersomes in structure) possessing multiple features, including nanosize, monodispersity, and incorporation of a phase-transitional imaging agent into the aqueous lumen. These features are not achievable via the conventional double-emulsion method for polymersome preparation. The nanospheres were constructed based on a novel triblock copolymer with dual pH sensitivity. The liquid-to-gas phase transition of the imaging agent induced by external low-frequency ultrasound may destroy the nanospheres for a rapid drug release, with simultaneous tissue-penetrating drug delivery inside a tumor. These effects may provide new opportunities for the development of an effective cancer therapy with few adverse effects. [ABSTRACT FROM AUTHOR]

Here we present a novel active surface that demonstrates pH responsiveness and can be used as a platform for designing ‘smart labels’. To generate our active surfaces, we immobilized polymer nanocompartments onto glass surfaces using thiol–ene chemistry. Prior to surface attachment, a pH responsive model dye was encapsulated within nanocompartments at two different pH values. We confirmed the attachment and distribution of dye‐loaded polymersomes and established the pH responsiveness of the active surface construct. The strategy presented here was carefully chosen to obtain small sized functional surfaces from commercially available materials that can be easily integrated into intelligent packaging systems. The ability to miniaturize such smart labels, while still being able to detect their response to the environment, is a crucial step towards developing active surfaces suitable for food packaging applications. [ABSTRACT FROM AUTHOR]

Next-generation therapeutic approaches are expected to rely on the engineering of biomimetic cellular systems that can mimic specific cellular functions. Herein, we demonstrate a highly effective route for constructing structural and functional eukaryotic cell mimics by loading pH-sensitive polymersomes as membrane-associated and free-floating organelle mimics inside the multifunctional cell membrane. Metabolism mimicry has been validated by performing successive enzymatic cascade reactions spatially separated at specific sites of cell mimics in the presence and absence of extracellular organelle mimics. These enzymatic reactions take place in a highly controllable, reproducible, efficient, and successive manner. Our biomimetic approach to material design for establishing functional principles brings considerable enrichment to the fields of biomedicine, biocatalysis, biotechnology, and systems biology. [ABSTRACT FROM AUTHOR]

Polymeric nanoreactors (NRs) have distinct advantages to improve chemical reaction efficiency, but the in vivo applications are limited by lack of tissue-specificity. Herein, novel glucose oxidase (GOD)-loaded therapeutic vesicular NRs ( theraNR) are constructed based on a diblock copolymer containing poly(ethylene glycol) (PEG) and copolymerized phenylboronic ester or piperidine-functionalized methacrylate (P(PBEM- co-PEM)). Upon systemic injection, theraNR are inactive in normal tissues. At a tumor site, theraNR are specifically activated by the tumor acidity via improved permeability of the membranes. Hydrogen peroxide (H2O2) production by the catalysis of GOD in theraNR increases tumor oxidative stress significantly. Meanwhile, high levels of H2O2 induce self-destruction of theraNR releasing quinone methide (QM) to deplete glutathione and suppress the antioxidant ability of cancer cells. Finally, theraNR efficiently kill cancer cells and ablate tumors via the synergistic effect. [ABSTRACT FROM AUTHOR]

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide-based block copolymer, poly(ethylene glycol)2000-poly(ε-caprolactone)6000-poly(glutamic acid)1000 (PEG2000-PCL6000-PGA1000), was investigated. The copolymer was synthesized via ring-opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self-assemble into aggregates and the critical aggregation concentrationwas 0.23 mg mL-1. Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox-loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH-responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST-1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48 h. The results also showed that PolyDox appeared to induce a higher anti-tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid-phase endocytosis pathway. [ABSTRACT FROM AUTHOR]

Choline phosphate (CP) as a novel zwitterion possesses specific and excellent properties compared with phosphorylcholine (PC), as well as its polymer, such as poly(2-(methacryloyloxy)ethyl choline phosphate) (PMCP), has been studied extensively due to its unique characteristics of rapid cellular internalization via the sepcial quadrupole interactions with the cell membrane. Recently, we reported a novel PMCP-based drug delivery system to enhance the cellular internalization where the drug was conjugated to the polymer via reversible acylhydrazone bond. Herein, to make full use of this feature of PMCP, we synthesized the diblock copolymer poly(2-(methacryloyloxy)ethyl choline phosphate)- b-poly(2-(diisopropylamino)ethyl methacrylate) (PMCP- b-PDPA), which could self-assemble into polymersomes with hydrophilic PMCP corona and hydrophobic membrane wall in mild conditions when the pH value is ≥ 6.4. It has been found that these polymersomes can be successfully used to load anticancer drug Dox with the loading content of about 11.30 wt%. After the polymersome is rapidly internalized by the cell with the aid of PMCP, the loaded drug can be burst-released in endosomes since PDPA segment is protonated at low pH environment, which renders PDPA to transfer from hydrophobic to hydrophilic, and the subsequent polymersomes collapse thoroughly. Ultimately, the 'proton sponge' effect of PDPA chain can further accelerate the Dox to escape from endosome to cytoplasm to exert cytostatic effects. Meanwhile, the cell viability assays showed that the Dox-loaded polymersomes exhibited significant inhibitory effect on tumor cells, indicating its great potential as a targeted intracellular delivery system with high efficiency. [ABSTRACT FROM AUTHOR]

Increasing complexity and diversity of polymersomes and their compartments is a key issue for mimicking cellular functions and protocells. Thus, new challenges arise in terms of achieving tunable membrane permeability and combining it with control over the membrane diffusion process, and thus enabling a localized and dynamic control of functionality and docking possibilities within or on the surface of polymeric compartments. This study reports the concept of polymersomes with pH-tunable membrane permeability for controlling sequential docking and undocking processes of small molecules and nanometer-sized protein mimics selectively on the inside and outside of the polymersome membrane as a further step toward the design of intelligent multifunctional compartments for use in synthetic biology and as protocells. Host-guest interactions between adamantane and β-cyclodextrin as well as noncovalent interactions between poly(ethylene glycol) tails and β-cyclodextrin are used to achieve selective and dynamic functionalization of the inner and outer spheres of the polymersome membrane. [ABSTRACT FROM AUTHOR]

Introduction: Intracellular delivery is a key step for many applications in medicine and for investigations into cellular function. This is particularly true for immunotherapy, which often requires controlled delivery of antigen and adjuvants to the cytoplasm of immune cells. Due to the complex responses generated by the stimulation of diverse immune cell populations, it is critical to monitor which cells are targeted during treatment. To address this issue, we have engineered an immunotheranostic polymersome delivery system that fluorescently marks immune cells following intracellular delivery. Methods: Amine functionalized poly(ethylene glycol)- bl-poly(propylene sulfide) (PEG-PPS-NH) was synthesized by anionic ring opening polymerization and bridged via perylene bisimide (PBI) to form a tetrablock copolymer (PEG-PPS-PBI-PPS-PEG). Block copolymers were assembled into polymersomes by thin film hydration in phosphate buffered saline and characterized by dynamic light scattering, cryogenic electron microscopy and fluorescence spectroscopy. Polymersomes were injected subcutaneously into the backs of mice, and draining lymph nodes were extracted for flow cytometric analysis of cellular uptake and disassembly. Results: Modular self-assembly of tetrablock/diblock copolymers in aqueous solutions induced π- π stacking of the PBI linker that both red-shifted and quenched the PBI fluorescence. Reactive oxygen species within the endosomes of phagocytic immune cell populations oxidized the PPS blocks, which disassembled the polymersomes for dequenching and shifting of the PBI fluorescence from 640 to 550 nm emission. Lymph node resident macrophages and dendritic cells were found to increase in 550 nm emission over the course of 3 days by flow cytometry. Conclusions: Immunotheranostic polymersomes present a versatile platform to probe the contributions of specific cell populations during the elicitation of controlled immune responses. Flanking PBI with two oxidation-sensitive hydrophobic PPS blocks enhanced π stacking and introduced a mechanism for disrupting π- π interactions to shift PBI fluorescence in response to oxidative conditions. Shifts from red (640 nm) to green (550 nm) fluorescence occurred in the presence of physiologically relevant concentrations of reactive oxygen species and could be observed within phagocytic cells both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to evaluate that the polymersomes (Ps- DOX- CA4P) dual-loaded with combretastatin-A4 phosphate ( CA4 P) and doxorubicin ( DOX) overcame drug resistance and sensitized tumour cells to chemotherapeutic drugs. Methods Ps- DOX- CA4P were prepared by solvent evaporation method using m PEG-b- PLA as carriers. The potential capability of CA4 P to reverse DOX resistance was verified by cytotoxicity test, apoptosis assay and cellular uptake of DOX. The comparison between free drugs and drug-loaded polymersomes was also made on a single-layer cell model and multicellular tumour spheroids to display the superiority of the drug vehicles. Furthermore, we put the emphasis on the investigation into underlying mechanisms for CA4 P overcoming DOX resistance. Key findings Results showed Ps- DOX- CA4P achieved increased uptake of DOX, enhanced cytotoxicity and apoptotic rate in MCF-7/ ADR cells as well as MCF-7/ ADR tumour spheroids. The potential molecular mechanisms may be related to inhibiting P-glycoprotein function by downregulating protein kinase Cα, stimulating ATPase activity, depleting ATP and increasing intracellular reactive oxygen species levels. Conclusions The findings validated the sensitization property of CA4 P on DOX independent of its well-known angiogenesis effect, which would provide a novel and promising strategy for drug-resistant cancer therapy. [ABSTRACT FROM AUTHOR]

We report molecular interaction-driven self-assembly of supramolecularly engineered amphiphilic macromolecules (SEAM) containing a single supramolecular structure-directing unit (SSDU) consisting of an H-bonding group connected to a naphthalene diimide chromophore. Two such SEAMs, P1-50 and P2-50, having the identical chemical structure and hydrophobic/hydrophilic balance, exhibit distinct self-assembled structures (polymersome and cylindrical micelle, respectively) due to a difference in the H-bonding group (hydrazide or amide, respectively) of the single SSDU. When mixed together, P1-50 and P2-50 adopted self-sorted assembly. For either series of polymers, variation in the hydrophobic/hydrophilic balance does not alter the morphology reconfirming that self-assembly is primarily driven by directional molecular interaction which is capable of overruling the existing norms in packing parameter-dependent morphology control in an immiscibility-driven block copolymer assembly. [ABSTRACT FROM AUTHOR]

We report molecular interaction-driven self-assembly of supramolecularly engineered amphiphilic macromolecules (SEAM) containing a single supramolecular structure-directing unit (SSDU) consisting of an H-bonding group connected to a naphthalene diimide chromophore. Two such SEAMs, P1-50 and P2-50, having the identical chemical structure and hydrophobic/hydrophilic balance, exhibit distinct self-assembled structures (polymersome and cylindrical micelle, respectively) due to a difference in the H-bonding group (hydrazide or amide, respectively) of the single SSDU. When mixed together, P1-50 and P2-50 adopted self-sorted assembly. For either series of polymers, variation in the hydrophobic/hydrophilic balance does not alter the morphology reconfirming that self-assembly is primarily driven by directional molecular interaction which is capable of overruling the existing norms in packing parameter-dependent morphology control in an immiscibility-driven block copolymer assembly. [ABSTRACT FROM AUTHOR]

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Simple cyclic disulfides under high tension mediate the uptake of giant substrates, that is, liposomes and polymersomes with diameters of up to 400 nm, into HeLa Kyoto cells. To place them at the surface of the vesicles, the strained disulfides were attached to the head-group of cationic amphiphiles. Bell-shaped dose response curves revealed self-activation of the strained amphiphiles by self-assembly into microdomains at low concentrations and self-inhibition by micelle formation at high concentrations. Poor colocalization of internalized vesicles with endosomes, lysosomes, and mitochondria indicate substantial release into the cytosol. The increasing activity with disulfide ring tension, inhibition with Ellman's reagent, and inactivity of maleimide and guanidinium controls outline a distinct mode of action that deserves further investigation and is promising for practical applications. [ABSTRACT FROM AUTHOR]

The light-triggered, programmable rupture of cell-sized vesicles is described, with particular emphasis on self-assembled polymersome capsules. The mechanism involves a hypotonic osmotic imbalance created by the accumulation of photogenerated species inside the lumen, which cannot be compensated owing to the low water permeability of the membrane. This simple and versatile mechanism can be adapted to a wealth of hydrosoluble molecules, which are either able to generate reactive oxygen species or undergo photocleavage. Ultimately, in a multi-compartmentalized and cell-like system, the possibility to selectively burst polymersomes with high specificity and temporal precision and to consequently deliver small encapsulated vesicles (both polymersomes and liposomes) is demonstrated. [ABSTRACT FROM AUTHOR]

Chemistry plays a crucial role in creating synthetic analogues of biomacromolecular structures. Of particular scientific and technological interest are biomimetic vesicles that are inspired by natural membrane compartments and organelles but avoid their drawbacks, such as membrane instability and limited control over cargo transport across the boundaries. In this study, completely synthetic vesicles were developed from stable polymeric walls and easy-to-engineer membrane DNA nanopores. The hybrid nanocontainers feature selective permeability and permit the transport of organic molecules of 1.5 nm size. Larger enzymes (ca. 5 nm) can be encapsulated and retained within the vesicles yet remain catalytically active. The hybrid structures constitute a new type of enzymatic nanoreactor. The high tunability of the polymeric vesicles and DNA pores will be key in tailoring the nanocontainers for applications in drug delivery, bioimaging, biocatalysis, and cell mimicry. [ABSTRACT FROM AUTHOR]

Nano-sized systems have been used extensively for the delivery of various therapeutics, such as pharmaceuticals, proteins, and nucleic acids. Exosomes are small extracellular vesicles secreted from parent cells by fusion of multivesicular late endosomes with the plasma membrane, which act as an intercellular communication mediator and contain bioactive molecules. Thus, exosomes may possess potential as a natural delivery system. Polymersomes are synthetic vesicles composed of external bilayers, typically generated from amphiphilic block copolymers, which resemble many aspects of exosomes and have been utilized widely in many drug delivery applications. In this review, general properties of exosomes and polymersomes and their recent applications in the drug delivery areas and potential in theranostic approaches are discussed. [ABSTRACT FROM AUTHOR]

Objective: Numerous researches have been conducted to comprehend the anti-cancer effects of curcumin (Cu). Although the anti-proliferative properties of Cu on cancerous cells is known, the clinical application of this gold substrate is limited. This limitation is mostly due to low solubility, inefficient bioavailability, rapid metabolism, and improper uptake. In this study, we have synthesized a novel biodegradable gemini surfactant (Gs), after which the curcumin (Cu) molecules were encapsulated within the polymer to overcome its physicochemical limitations. Methods: We prepared Gs-Cu nanoparticles by the nanoprecipitation method. Size and polydispersity index of the nanoparticles were determined by the dynamic light scattering (DLS) technique. The release profile of Cu from the polymer matrix was studied, and the MTT assay and cellular uptake of Gs-Cu on MDA-MB-231 cells were investigated in vitro. Results: The Gs polymer had the capability to form polymersomes in an aqueous solution; a narrow size distribution was obtained (PDI≅0.3). The encapsulation efficiency approximated 87%. We observed a sustained release profile due to incorporation of Cu into the polymer matrix. The Gs-Cu complex showed more cytotoxicity compared to free Cu because of the higher rate of cellular internalization. Conclusions: The data indicate that Gs polymersomes can be regarded as nanocarriers for hydrophobic curcumin molecules. [ABSTRACT FROM AUTHOR]

Purpose: To develop a technique that maximizes the encapsulation of functional proteins within neutrally charged, fully PEGylated and nanoscale polymer vesicles (i.e., polymersomes). Methods: Three conventional vesicle formation methods were utilized for encapsulation of myoglobin (Mb) in polymersomes of varying size, PEG length, and membrane thickness. Mb concentrations were monitored by UV-Vis spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP-OES) and by the bicinchoninic acid (BCA) assay. Suspensions were subject to protease treatment to differentiate the amounts of surface-associated vs. encapsulated Mb. Polymersome sizes and morphologies were monitored by dynamic light scattering (DLS) and by cryogenic transmission electron microscopy (cryo-TEM), respectively. Binding and release of oxygen were measured using a Hemeox analyzer. Results: Using the established 'thin-film rehydration' and 'direct hydration' methods, Mb was found to be largely surface-associated with negligible aqueous encapsulation within polymersome suspensions. Through iterative optimization, a novel 'progressive saturation' technique was developed that greatly increased the final concentrations of Mb (from < 0.5 to > 2.0 mg/mL in solution), the final weight ratio of Mb-to-polymer that could be reproducibly obtained (from < 1 to > 4 w/w% Mb/polymer), as well as the overall efficiency of Mb encapsulation (from < 5 to > 90%). Stable vesicle morphologies were verified by cryo-TEM; the suspensions also displayed no signs of aggregate formation for > 2 weeks as assessed by DLS. 'Progressive saturation' was further utilized for the encapsulation of a variety of other proteins, ranging in size from 17 to 450 kDa. Conclusions: Compared to established vesicle formation methods, 'progressive saturation' increases the quantities of functional proteins that may be encapsulated in nanoscale polymersomes. [ABSTRACT FROM AUTHOR]

ABSTRACT The article describes synthesis and thermally triggered self-assembly of a Poly (ethylene oxide)- block-poly ( N-insopropylacrylamide) (PEO- b-PNIPAm) in aqueous medium. At rt, the polymer remains as unimer, however, at lower critical solution temperature (LCST) of PNIPAm (32 °C), it forms a rather large undefined aggregate which at slightly elevated temperature (∼40 °C) converges to well defined polymersome structure (Critical aggregation concentration = 0.45 mg/mL) with hydrodynamic diameter of 40-50 nm. By lowering the temperature, initial swelling of the compact vesicle followed by reversible disassembly to unimer was noticed. The polymersome exhibits encapsulation ability to a hydrophilic dye Calcein which can be spontaneously released by lowering the temperature below cloud point. Likewise a hydrophobic dye namely 8-Anilino-1-naphthalenesulfonic acid (ANS) can also be encapsulated and released by thermal trigger. Detail photoluminescence studies reveal ANS dye can be used as a generalized probe molecule for detecting LCST of a thermoresponsive polymer by 'fluorescence on' above LCST even by cursory observation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2444-2451 [ABSTRACT FROM AUTHOR]

There has been increasing interest in utilizing bottom-up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing 'hybrid' artificial cells. This Concept article covers recent advances and the current state-of-the-art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology. [ABSTRACT FROM AUTHOR]