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Amphiphilic block copolymers are common materials used for the fabrication of various nanostructures with biomedical applications including nanocapsules, nanospheres, micelles and polymeric vesicles. According to the literature, polymersomes have several advantages compared to other nanostructures used as drug delivery systems comprising better stability, facile synthesis, prolonged circulation time, and passive/active targeting capability. Various types of nanoparticles are formed by varying the ratio of the hydrophobic/hydrophilic blocks. Changing hydrophobic/hydrophilic ratio of amphiphilic block copolymers has an impact on the structural characteristics of polymers such as changing molecular weight and surface functionalization of the block copolymer. Thus, polymerization strategies are an important factor that influences polymersomes quality. In this review, different polymerization strategies for the synthesis of block copolymers applied in polymersomes formation, are described.

Nano drug delivery systems have attracted researchers' growing attention and are gradually emerging into the public views. More and more nano-formulations are being approved for marketing or clinical use, representing the field's booming development. Copolymer self-assembly systems such as micelles, nanoparticles, polymersomes occupy a prominent position in the field of nano-drug delivery carriers. Among them, polymersomes, unlike micelles or nanoparticles, resemble liposomes' structure and possess large internal hollow hydrophilic reservoirs, allowing them to carry hydrophilic drugs. Nevertheless, their insufficient drug loading efficiency and unruly self-assembly morphology have somewhat constrained their applications. Especially for the delivery of biomacromolecule such as peptides, the encapsulation efficiency is always considered to be a formidable obstacle, even if the enormous hydrophilic core would render the polymersomes to have considerable potential in this regard. Reassuringly, the emergence of asymmetric polymersomes holds the prospect of solving this problem. With the development of synthetic technology and a deeper understanding of the self-assembly process, the asymmetric polymersomes which are with different inner and outer shell composition have been gradually recognized by researchers. It has made possible elevated drug loading, more controllable assembly processes and release performance. The internal hydrophilic blocks different from the outer shell could be engineered to have a more remarkable affinity to the cargos or could contain a non-watery aqueous phase to enable the thermodynamically preferred encapsulation of cargos, which would allow for a substantial improvement in drug encapsulation efficiency compared to the conventional approach. In this paper, we aim to deepen the understanding to asymmetric polymersomes and lay the foundation for the development of this field by describing four main elements: the mechanism of their preparation and asymmetric membrane formation process, the characterization of asymmetric membranes, the efficient drug loading, and the special stimulus-responsive release mechanism.

Embargado hasta 09/04/2023 Polymersomes and related self-assembled nanostructures displaying Aggregation-Induced Emission (AIE) are highly relevant for plenty of applications in imaging, biology and functional devices. Experimentally simple, scalable and universal strategies for on-demand self-assembly of polymers rendering well-defined nanostructures are highly desirable. A purposefully designed combination of amphiphilic block copolymers including tunable lengths of hydrophilic polyethylene glycol (PEGm) and hydrophobic AIE polymer poly(tetraphenylethylene-trimethylenecarbonate) (P(TPE-TMC)n) has been studied at the air/liquid interface. The unique 2D assembly properties have been analyzed by thermodynamic measurements, UV-vis reflection spectroscopy and photoluminescence in combination with molecular dynamics simulations. The (PEG)m-b-P(TPE-TMC)n monolayers formed tunable 2D nanostructures self-assembled on demand by adjusting the available surface area. Tuning of the PEG length allows to modification of the area per polymer molecule at the air/liquid interface. Molecular detail on the arrangement of the polymer molecules and relevant molecular interactions has been convincingly described. AIE fluorescence at the air/liquid interface has been successfully achieved by the (PEG)m-b-P(TPE-TMC)n nanostructures. An experimentally simple 2D to 3D transition allowed to obtain 3D polymersomes in solution. This work suggests that engineered amphiphilic polymers for AIE may be suitable for selective 2D and 3D self-assembly for imaging and technological applications.

This manuscript describes fabrication of a cross-linked and nanoengineered three-dimensional matrix of polymersomes for encapsulation of macromolecular cargo such as enzymes. Our approach involves the integration of glucose oxidase (GOx) enzyme into networks of a polysaccharide-silica matrix. Direct chemical cross-linking occurs between the residual groups of alginate polymer and the alkoxysilane moieties in a palladium nanoparticle dispersion; a transformation in the chemical configuration of the alginate hydrogel along with precise control over the pore size distribution facilitate immobilization of enzyme. The activity of the polymersomes was evaluated by enzymatic oxidation of the glucose substrate in phosphate buffer through loading different concentrations of GOx. In situ generated H2O2 was decomposed by the as-synthesized Prussian blue nanoparticles, which serve as an excellent peroxidase mimetic. The functional enzyme polymersome system was utilized for in vitro detection of blood glucose values.

Biomembrane curvature formation has long been observed to be essential in the change of membrane morphology and intracellular processes. The significant importance of curvature formation has attracted scientists from different backgrounds to study it. Although magnificent progress has been achieved using liposome models, the instability of these models restrict further exploration. Here, we report a new approach to mimic biomembrane curvature formation using polymersomes as a model, and poly(N-isopropylacrylamide) to induce the local curvature based on its co-nonsolvency phenomenon. Curvatures form when poly(N-isopropylacrylamide) becomes hydrophobic and inserts into the membrane through solvent addition. The insertion area can be fine-tuned by adjusting the poly(N-isopropylacrylamide) concentration, accompanied by the formation of new polymersome-based non-axisymmetric shapes. Moreover, a systematic view of curvature formation is provided through investigation of the segregation, local distribution and dissociation of inserted poly(N-isopropylacrylamide). This strategy successfully mimicks biomembrane curvature formation in polymersomes and a detailed observation of the insertion can be beneficial for a further understanding of the curvature formation process. Furthermore, polymer insertion induced shape changing could open up new routes for the design of non-axisymmetric nanocarriers and nanomachines to enrich the boundless possibilities of nanotechnology., Investigating biomembrane curvature formation is important for studying intracellular processes, but the instability of liposome models mimicking these membranes restricts exploration of membrane processes. Here, the authors demonstrate control over the curvature formation in polymersome membranes by insertion of PNIPAm as stimuli responsive polymer.

The emergence of smart tubular vesicles has attracted increasing attention in the fields of life science and nanoengineering. Recent preliminary efforts have been put into fabricating kinds of smart tubular vesicles with different morphologies via the self-assembly of amphiphilic azobenzene-containing block copolymers. However, the detailed environmental effects on their self-assembly behaviors in solution remain uncharted. In this work, we carefully investigated several external factors that could influence the morphology formation and the transition of azobenzene-containing tubular vesicles, including the initial polymer concentration, the nature of common solvent, temperature, water addition rate, and irradiation with light of different wavelengths. The result showed that the morphological modulation of these tubular polymersomes was synergistically controlled by these external factors from both thermodynamics and kinetics aspects. This study could be helpful to understand and illustrate the morphology formation and modulation of smart tubular polymersomes.

Polymersomes frequently appear in the literature as promising candidates for a wide range of applications from targeted drug delivery to nanoreactors. From a cell mimetic point of view, it is important to understand the size and shape changes of the vesicles in the physiological environment since that can influence the drug delivery mechanism. In this work we studied the structural features of polymersomes consisting of poly(ethylene glycol)-poly(dimethylsiloxane)-poly(ethylene glycol) at the nanoscopic length scale in the presence of NaCl, which is a very common molecule in the biotic aqueous environment. We used dynamic light scattering (DLS), cryo-TEM, small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS). We observed transformation of polymersomes from spherical to elongated vesicles at low salt concentration and into multivesicular structures at high salt concentration. Model fitting analysis of SANS data indicated a reduction of vesicle radius up to 47% and from the SAXS data we observed an increase in membrane thickness up to 8% and an increase of the PDMS hydrophobic segment up to 11% indicating stretching of the membrane due to osmotic imbalance. Also, from the increase in the interlamellar repeat distance up to 98% under high salt concentrations, we concluded that the shape and structural changes observed in the polymersomes are a combined result of osmotic pressure change and ion-membrane interactions.

We report an efficient one-pot synthesis of a new biocompatible amphiphilic ABC triblock terpolymer: poly(ethylene oxide)- block -poly(2-(3-ethylheptyl)-2-oxazoline)- block -poly(2-ethyl-2-oxazoline) (PEO- b -PEHOx- b -PEtOz) using sequential microwave-assisted polymerization. Depending on the hydrophilic weight fraction of the terpolymers, nanoscopic micelles, worms, and polymersomes, as well as multicompartment vesicles, were formed. The self-assemblies were thoroughly analyzed regarding their size and shape using dynamic and static light scattering, TEM, and cryogenic TEM. By varying the ratio of PEO to PEtOz, we were able to drive the asymmetry of the polymersome membranes, which was proved by two independent methods, bicinchoninic acid assay and 2D- 1 H-NOESY NMR spectroscopy, which confirmed the presence of a longer PEO block (45 units) and the absence of a shorter PEtOz (less than 32 units) on the outer surface of the polymersomes. Thus, from this new family of ABC triblock terpolymers, asymmetric polymersomes with a thin membrane (6-10 nm) can be obtained, justifying the potential use in biomedical applications with the direct insertion of transmembrane proteins.

Polymersomes are a class of synthetic vesicles composed of a polymer membrane surrounding an aqueous inner cavity. In addition to their overall size, the thickness and composition of polymersome membranes determine the range of potential applications in which they can be employed. While synthetic polymer chemists have made great strides in controlling polymersome membrane parameters, measurement of their permeability to various analytes including gases, ions, organic molecules, and macromolecules remains a significant challenge. In this Outlook, we compare the general methods that have been developed to quantify polymersome membrane permeability, focusing in particular on their capability to accurately measure analyte flux. In addition, we briefly highlight strategies to control membrane permeability. Based on these learnings, we propose a set of criteria for designing future methods of quantifying membrane permeability such that the passage of a variety of molecules into and out of their lumens can be better understood., Herein, we discuss the recent advances in methods to quantify polymersome membrane permeability and propose five key principles to facilitate future developments of new, more quantitative strategies.

Block copolymer polymersomes offer considerable access for applications in a variety of fields; however, the traditional cosolvent self-assembly method can only produce polymersomes at a low solids...

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.

The effect of the hydrophobic block length on the morphologies of polymerization-induced self-assembled (PISA) nanoparticles is well understood. However, the influence of drug loading on the phase morphology of the nanoparticles during the PISA process, and the resulting biological function of PISA nanoparticles, has barely been investigated. In this work, we show that the addition of a drug, curcumin, during the PISA process shifts the phase diagram toward different morphologies. The PISA system was based on hydrophilic poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC), which was chain extended with hydrophobic methyl methacrylate (MMA) in various concentrations of curcumin. According to transmission electron microscopy, the presence of curcumin led to the transition of, for example, worms to polymersome and micelles to worms analysis. To understand the interaction between polymer particles and drug, small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and fluorescence lifetime measurements were carried out. These measurements show that curcumin is predominantly located in the core in the case of micelles and worms while it is found in the shell of polymersomes. The change in morphology influences the cellular uptake by MCF-7 cells and the movement of the particles in multicellular cancer spheroids (3D model). With the increasing amount of drug, the cellular uptake of micelles and worms was enhanced with the increasing grafting density of MPC chains, which contrasts the decreasing cellular uptake in the higher drug-loaded polymersomes due to the lower shell hydration.

Polymersomes (also known as polymer vesicles) are hollow nanoparticles (comprising a lumen, a membrane and inner and outer coronas) which are considered as promising candidates for biomedical applications such as controlled drug release, gene delivery, cell mimicking, highly efficient antibacterial treatment and cancer theranostics. Conventional synthetic polymersomes are composed of a dense homogeneous membrane, identical inner and outer coronas and spatially-separated functional substructures. In comparison to bio-membranes (or cellular membranes), the characteristics of synthetic membranes are often insufficient to meet the requirements for biomedical applications, making such polymersomes inefficient or even incapable for such duties. It is still a challenge for synthetic polymersomes to achieve efficient trans-membrane trafficking of macromolecules, different functionalization between inner and outer coronas, or efficient synergy of functions between their coronas and membranes. The lack of these characteristics therefore inhibits gene delivery, theranostic applications and antibacterial properties. To investigate and ultimately improve the above-mentioned properties of polymersomes, we focus on three different types of polymersome structures: (1) Polymersomes with inhomogeneous membranes, where the membrane is composed of different micro-phases with various functions; (2) polymersomes with asymmetrical coronas, whose inner coronas differ from outer coronas in chemical composition, or have different modifications; (3) polymersomes with fused membranes and coronas, where the membrane and coronas become fused and thus function together. These three polymersomes allow specific biomedical applications and provide new design strategies for their clinical applications. Herein, we review the related research which assesses the membrane structures and preparation strategies of the above polymersomes. Finally, we summarize the design principles and possible biomedical applications of the polymersomes with the various structures. For polymersomes with inhomogeneous membranes: The membrane structure is mainly attributed to micro-phase separation, and cross-linking can be used to initiate the micro-phase separation process. This is because of the high chain flexibility of the polymer which results into a modularly functionalized polymersome membrane. For polymersomes with asymmetrical coronas: The structure mainly results from the different block volumes between the inner and outer coronas (located within the lumen and surface of the polymersome, respectively). The hydrophilic block with a lower volume faces the lumen, while the block with a larger volume is located on the outer surface of the polymersome. For polymersomes with fused membranes and coronas: The polymer, with various architectures (such as alternating polymer, statistical polymer or even homopolymer), congregates the membrane-forming and corona-forming polymer segments. This leads to an enhanced synergy during clinical applications. In summary, the design of polymersome structures involves different aspects from both polymer and phase structures. Biomedical practices or clinical translations require materials which are biocompatible, controlled-biodegradable, available by mass production, etc. Future polymersomes will be more suitable for clinical practices, and are therefore promising for biomedical applications.

Cancer cells have reductive and acidic environments as compared to the normal body cells. Development of reductive/acidic responsive polymersomes will play a major role in cancer therapy to trigger the release of the loaded drug. In our work, we synthesized three different reductive/acidic dual-responsive polymers, poly[(mPEG-SS-amino) (N,N-diisopropylethylenediamino)phosphazenes] (PPDPs) in different mole ratios of side groups. These PPDPs were characterized by 1H NMR, 31P NMR, FT-IR and GPC. After that, the PPDPs were allowed to self-assemble into drug-loaded polymersomes with high loading content and encapsulation efficiency of hydrophilic/hydrophobic anticancer drugs. The hydrophilic anticancer drug doxorubicin hydrochloride (DOX·HCl) and hydrophobic drug doxorubicin were used. These PPDPs-based polymersomes showed reductive/acidic stimuli-responsive release of anticancer drugs. Moreover, these polymersomes also exhibited suitable hydrodynamic diameters, which will facilitate the longtime circulation in bloodstream due to avoiding renal clearance and close contact to the tumor cells in vascular sections due to enhanced permeability and retention effect. Collectively, these developed polymersomes may provide an effective platform for anticancer drugs delivery.

One of the hallmarks of nature is compartmentalization, and natural cell membranes are often asymmetric in terms of the inner and outer side. This communication describes work toward synthesizing such an asymmetric membrane from the bottom-up. A family of amphiphilic di- and triblock copolymers were synthesized via Cu(0)-mediated single electron transfer-living radical polymerization with the aim to generate polymer vesicles, or polymersomes, with an asymmetric membrane. Self-assembly of these polymeric amphiphiles in aqueous media was investigated using asymmetric field-flow fractionation and cryo-electron microscopy. Utilizing mixtures of diblock copolymers with differing hydrophilic moieties resulted in the formation of vesicles with an asymmetric segregation of charge between the inner and outer leaflet, confirmed by zeta potential measurements. These polymers, synthesized in good yields and using a biologically compatible method to induce self-assembly, have a promising range of applications from nanomedicine to synthetic cell research.

Polymers containing organoboronic acids have recently gained interest as sugar-responsive materials owing to the reversible binding of saccharides to boronic acids, which triggers a change in the physical and chemical properties of these polymers, such as their water solubility. In particular, the ability of these polymers to bind glucose has attracted considerable attention because of the promise of these materials for the development of sensors and drug delivery systems for glucose-related human diseases, such as diabetes. We report here a new class of sugar-responsive polymers that are based on a sequence-specific copolymer of styreneboroxole and N-functionalized maleimide. The reversible addition–fragmentation and chain transfer (RAFT) polymerization of this pair of monomers ensured that a glucose receptor alternates with a nonresponsive solubilizing group throughout the sugar-responsive polymer chain. Due to the presence of hydrophilic solubilizing groups beween the solubility-switching boroxole moie...

Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a smart drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up core-shell UCNPs with a shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm. An amphiphilic block copolymer with UV-responsive

Vesicles constructed of either synthetic polymers alone (polymersomes) or a combination of polymers and lipids (lipo-polymersomes) demonstrate excellent long-term stability and ability to integrate membrane proteins. Applications using lipo-polymersomes with integrated membrane proteins require suitable supports to maintain protein functionality. Using lipo-polymersomes loaded with the light-driven proton pump bacteriorhodopsin (BR), we demonstrate here how the photocurrent is influenced by a chosen support. In our study, we deposited BR-loaded lipo-polymersomes in a cross-linked polyelectrolyte multilayer assembly either directly physisorbed on gold electrode microchips or cross-linked on an intermediary polyethersulfone (PES) membrane covalently grafted using a hydrogel cushion. In both cases, electrochemical impedance spectroscopic characterization demonstrated successful polyelectrolyte assembly with BR-loaded lipo-polymersomes. Light-induced proton pumping by BR-loaded lipo-polymersomes in the different support constructs was characterized by amperometric recording of the generated photocurrent. Application of the hydrogel/PES membrane support together with the polyelectrolyte assembly decreased the transient current response upon light activation of BR, while enhancing the generated stationary current to over 700 nA/cm2. On the other hand, the current response from BR-loaded lipo-polymersomes in a polyelectrolyte assembly without the hydrogel/PES membrane support was primarily a transient peak combined with a low-nanoampere-level stationary photocurrent. Hence, the obtained results demonstrated that by using a hydrogel/PES support it was feasible to monitor continuously light-induced proton flux in biomimetic applications of lipo-polymersomes.

We herein demonstrate the outstanding protein-repelling characteristic of star-like micelles and polymersomes manufactured from amphiphilic block copolymers made by poly(butylene oxide) (PBO) hydrophobic segments and polyglycidol (PGL) hydrophilic outer shells. Although positively charged proteins (herein modeled by lysozyme) may adsorb onto the surface of micelles and polymersomes where the assemblies are stabilized by short PGL chains (degree of polymerization smaller than 15), the protein adsorption vanishes when the degree of polymerization of the hydrophilic segment (PGL) is higher than ∼20, regardless the morphology. This has been probed by using three different model proteins which are remarkably different concerning molecular weight, size, and zeta potential (bovine serum albumin (BSA), lysozyme, and immunoglobulin G (IgG)). Indeed, the adsorption of the most abundant plasma protein (herein modeled as BSA) is circumvented even by using very short PGL shells due to the highly negative zeta potential of the produced assemblies which presumably promote protein-nanoparticle electrostatic repulsion. The negative zeta potential, on the other hand, enables lysozyme adsorption, and the phenomenon is governed by electrostatic forces as evidenced by isothermal titration calorimetry. Nevertheless, the protein coating can be circumvented by slightly increasing the degree of polymerization of the hydrophilic segment. Notably, the PGL length required to circumvent protein fouling is significantly smaller than the one required for PEO. This feature and the safety concerns regarding the synthetic procedures on the preparation of poly(ethylene oxide)-based amphiphilic copolymers might make polyglycidol a promising alternative toward the production of nonfouling spherical particles.

Dengue virus (DENV) is a major infectious viral pathogen that affects millions of individuals worldwide every year, causing a potentially fatal syndrome, while no commercial antiviral drugs are yet available. To develop an antiviral against dengue fever, it is necessary to understand the relationship between DENV and host cells, which could provide a basis for viral dynamics and identification of inhibitory drug targets. In this study, we designed DiD-loaded and BODIPY-ceramide-encapsulated DENV-polymersome hybrid nanovesicles (DENVSomes) prepared by an extrusion method, which trigger red fluorescence in the endosome and green in the Golgi. DENVSome monitors the dynamics of host cell-virus interaction and tracking in living cells with novel state-of-the-art imaging technologies that show images at high resolution. Also, DENVSome can be exploited to screen whether candidate antiviral drugs interact with DENVs. Consequently, we successfully demonstrated that DENVSome is an efficient tool for tracking and unraveling the mechanisms of replication and drug screening for antiviral drugs of DENV.

The assembly of amphiphilic block copolymers in well-defined polymer nanoparticles is an intricate interplay between polymer composition, method of assembly and the properties of the organic solvent used to dissolve the polymer building blocks. Remarkably, the role of organic solvent composition has been much less studied in comparison to the other two parameters. Here we have systematically investigated the effect of organic solvent composition, namely, the ratio between tetrahydrofuran and dioxane, on the self-assembly of PEG-PDLLA copolymers into polymer vesicles and their subsequent shape change in different topologies. Uncovering such physical basis unlocks new opportunities for the development of complex nanoparticles without the need of extended polymer engineering processes.

Polymeric vesicles (polymersomes) are an important class of nanoparticles for various biomedical applications. Their interaction with biological systems is strongly dependent on their topological features such as size, shape and surface charge. We have recently developed a versatile method that enables the formation of tubes or bowl-shaped vesicles (stomatocytes) out of spherical vesicles composed of the biodegradable block copolymer poly(ethylene glycol)-poly(D,L-lactic acid) (PEG-b-PDLLA), via a dialysis process. Applying this method for particles with different surface charge is however a far from trivial task, as the shape change process is affected by spontaneous membrane curvature, which is strongly influenced by the presence of charged polymer end groups. Here we describe an optimized procedure to attain an effective shape transformation toward tubes of PEG-b-PDLLA polymersomes containing PEG blocks with amine (A) or carboxylic acid (CA) end groups. The salt concentration employed during the dialysis process turns out to be key, with the CA-polymersomes requiring substantially lower concentrations than unmodified or A-ones. The ability to control now reliably shape and surface charge in these polymer vesicles, allows a future systematic analysis of the effect of these topological parameters on the biological response of the nanoparticles.

International audience; Understanding the interactions between nanoparticles (NPs) and boundaries of cells is crucial both for their toxicity and therapeutic applications. Besides specific receptor-mediated endocytosis of surface-functionalized NPs, passive internalization is prompted by relatively unspecific parameters, such as particle size and charge. Based on theoretical treatments, adhesion to and bending of the cell membrane can induce NP wrapping. Experimentally, powerful tools are needed to selectively probe possible membrane-NP motifs at very dilute conditions and avoid dye labeling. In this work, we employ surface resonance-enhanced dynamic light scattering, surface plasmon resonance, electron microscopy, and simulations for sensing interactions between plasmonic AuNPs and polymersomes. We distinguish three different interaction scenarios at nanomolar concentrations by tuning the surface charge of AuNPs and rationalize these events by balancing vesicle bending and electrostatic/van der Waals AuNP and vesicle adhesion. The clarification of the physical conditions under which nanoparticles passively translocate across membranes can aid in the rational design of drugs that cannot exploit specific modes of cellular uptake and also elucidates physical properties that render nanoparticles in the environment particularly toxic.

Light-triggered unique shape transformation of calcein-loaded giant polymersomes with tubular protrusions, which serve as a reservoir membrane area during the shape transformation, is reported here. Under irradiation at the excitation wavelength of calcein, the tubular protrusions form strings of budded vesicles and then reintegrate into the mother vesicle. The initial giant polymersomes transform to two connected spherical vesicles via two pathways to alleviate the osmotic pressure imbalance across the vesicle membrane. The two connected spherical vesicles further transform to a mother vesicle with an inner daughter vesicle after switching off the light to relieve the bending energy. The finding provides a promising platform to mimic cell morphology changes.

Prevention of metastatic and local-regional recurrence of cancer after surgery remains difficult. Targeting postsurgical premetastatic niche and microresiduals presents an excellent prospective opportunity but is often challenged by poor therapeutic delivery into minimal residual tumors. Here, an enzymatically transformable polymer-based nanotherapeutic approach is presented that exploits matrix metalloproteinase (MMP) overactivation in tumor-associated tissues to guide the codelivery of colchicine (microtubule-disrupting and anti-inflammatory agent) and marimastat (MMP inhibitor). The dePEGylation of polymersomes catalyzed by MMPs not only exposes the guanidine moiety to improve tissue/cell-targeting/retention to increase bioavailability, but also differentially releases marimastat and colchicine to engage their extracellular (MMPs) and intracellular (microtubules) targets of action, respectively. In primary tumors/overt metastases, the vasculature-specific targeting of nanotherapeutics can function synchronously with the enhanced permeability and retention effect to deter malignant progression of metastatic breast cancer. After the surgical removal of large primary tumors, nanotherapeutic agents are localized in the premetastatic niche and at the site of the postsurgical wound, disrupting the premetastatic microenvironment and eliminating microresiduals, which radically reduces metastatic and local-regional recurrence. The findings suggest that nanotherapeutics can safely widen the therapeutic window to resuscitate colchicine and MMP inhibitors for other inflammatory disorders.

In nature, biochemical reactions often take place in confined spaces, as typically exemplified by cells. As numerous cellular reactors can be integrated to maintain the living system, researchers have made constant efforts to construct cell-like structures for achieving similar transformations in vitro. Micro/nano reactors engineered by polymers and colloids are becoming popular and being applied in many fields, especially there has been an increasing trend toward constructing metal-organic framework (MOF) micro/nano reactors with the thriving of MOF nanotechnologies. Because of the uniform pores of MOFs, the transmission of substances can be regulated more accurately. Along with properties of large specific surface area, functional diversity and precise control of the particle size, MOFs are also ideal platforms for building distinct microenvironments for biological substances. Compared with traditional polymersomes and colloidosomes, the unique characteristics of MOFs render them potent micro/nano reactor shell materials, mimicking cells for applications in enzymatic catalysis, sensing, nanotherapy, vaccine, biodegradation, etc. This review highlights recent signs of progress on the design of MOF micro/nano reactors and their applications in biology, discusses the existing problems, and prospects their promising properties for smarter multifunctional applications.

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T cell (Treg) activation. Here, we engineered the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to selectively target and modulate DCs by transporting the anti-inflammatory agent 1, 25-Dihydroxyvitamin D3 (aVD) and ApoB-100 derived antigenic peptide P210. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhanced the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Intravenous administration of the optimized polymersomes achieved selective targeting of DCs in atheroma and spleen compared to all other cell populations, including both immune and CD45(−) cells, and locally increased the presence of tolerogenic DCs and cytokines. aVD-loaded polymersomes significantly inhibited atherosclerotic lesion development in high fat diet-fed ApoE(−/−) mice following 8 weeks of administration. Incorporation of the P210 peptide generated the largest reductions in vascular lesion area (~33%, p

Membrane structuration of Large Hybrid Unilamellar Polymer/Lipid Vesicle (LHUV) is an important parameter on the optimization of their properties and thus their valuation in various fields. However, this kind of information is hardly accessible. In this work, we will focus on the development of LHUV obtained from the self-assembly of diblock poly(dimethylsiloxane)-b-poly(ethylene oxide) (PDMS-b-PEO) of different molar masses combined with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at 15% and 25% w/w content. The hybrid character of the resulting vesicles as well as their membrane structure are characterized by the mean of different techniques such as small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). We show that hybrid vesicles with homogeneous membrane structure are obtained whatever the molar mass of the block copolymer (from 2500 to 4000 g/mol), with of a small number of tubular structures observed with the higher molar mass. We also demonstrate that the permeability of the LHUV, evaluated through controlled release experiments of fluorescein loaded in LHUV, is essentially controlled by the lipid/polymer composition.

Polymersomes are multicompartmental vesicular nano-objects obtained by self-assembly of amphiphilic copolymers. When prepared in the aqueous phase, they are composed of a hydrophobic bilayer enclosing water. Although such fascinating polymeric nano-objects have been widely reported with synthetic block copolymers, their formation from polysaccharide-based copolymers remains a significant challenge. In the present study, the powerful platform technology known as polymerization-induced self-assembly was used to prepare in situ pure vesicles from a polysaccharide-grafted copolymer: dextran-g-poly(2-hydroxypropyl methacrylate) (Dex-g-PHPMA). The growth of the PHPMA grafts was performed with a dextran-based macromolecular chain transfer agent in water at 20 °C using photomediated reversible addition fragmentation chain transfer polymerization at 405 nm. Transmission electron microscopy, cryogenic electron microscopy, small-angle X-ray scattering, atomic force microscopy, and dynamic light scattering revealed that amphiphilic Dex-g-PHPMAX = 100-300 (X is the targeted average degree of polymerization, Xn, of each graft at full conversion) exhibit remarkable self-assembly behavior. On the one hand, vesicles were obtained over a wide range of solid concentrations (from 2.5% to 13.5% w/w), which can facilitate posterior targeting of such rare morphology. On the other hand, the extension of Xn induces an increase in the vesicle membrane thickness, rather than a morphological evolution (spherical micelles to cylinders to vesicles).

Solid supported polymer membranes as scaffold for the insertion of functional biomolecules provide the basis for mimicking natural membranes. They also provide the means for unraveling biomolecule-membrane interactions and engineering platforms for biosensing. Vesicle fusion is an established procedure to obtain solid supported lipid bilayers but the more robust polymer vesicles tend to resist fusion and planar membranes rarely form. Here, we build on vesicle fusion to develop a refined and efficient way to produce solid supported membranes based on poly(dimethylsiloxane)-poly(2-methyl-2-oxazoline) (PMOXA-b-PDMS-b-PMOXA) amphiphilic triblock copolymers. We first create thiol-bearing polymer vesicles (polymersomes) and anchor them on a gold substrate. An osmotic shock then provokes polymersome rupture and drives planar film formation. Prerequisite for a uniform amphiphilic planar membrane is the proper combination of immobilized polymersomes and osmotic shock conditions. Thus, we explored the impact of the hydrophobic PDMS block length of the polymersome on the formation and the characteristics of the resulting solid supported polymer assemblies by quarz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM) and spectroscopic ellipsometry (SE). When the PDMS block is short enough, attached polymersomes restructure in response to osmotic shock, resulting in a uniform planar membrane. Our approach to rapidly form planar polymer membranes by vesicle fusion brings many advantages to the development of synthetic planar membranes for bio-sensing and biotechnological applications.

Polymersomes are membrane-bound, bilayer vesicles created from amphiphilic block copolymers that can encapsulate both hydrophobic and hydrophilic payloads for drug delivery applications. Despite their promise, polymersomes are limited in application due to their spherical shape, which is not readily taken up by cells, as demonstrated by solid nanoparticle scientists. This article describes a salt-based method for increasing the aspect ratios of spherical poly(ethylene glycol) (PEG)- based polymersomes. This method can elongate polymersomes and ultimately control their final shape by adding sodium chloride in post-formation dialysis. Salt concentration can be varied, as described in this method, based on the hydrophobicity of the block copolymer being used as the base for the polymersome and the target shape. Elongated nanoparticles have the potential to better target the endothelium in larger diameter blood vessels, like veins, where margination is observed. This protocol can expand therapeutic nanoparticle applications by utilizing elongation techniques in tandem with the dual-loading, long-circulating benefits of polymersomes.

ObjectiveResearches proving methods for nano encapsulation of neonatal porcine islet-like cell clusters (NPCCs) using polymersomes (PSomes) formed using polymers of polyethylene glycol-block-poly lactide (PEG-b-PLA). Herein, our studies present efficient nano encapsulation procedure with minimal damage and loss of NPCCs. MethodsWe used N-hydroxysuccinimide (NHS) on the N-terminal of PSomes to induce binding of amine groups in the extracellular matrix surrounding NPCCs. F-10 culture medium with bovine serum albumin was used in the nano-encapsulation procedure to minimize damage and loss of NPCCs. Finally, we induced crosslinking between bi-functional PSomes (NHS-/NH2-PSomes). ResultsF-10 culture medium containing 0.25% BSA with pH of 7.3 minimized the damage and loss of NPCCs after nano-encapsulation as compared with using basic HBSS buffer (pH 8.0). Also, we induced the efficiency nano encapsulation through conjugation of PSomes using bi-functional PSomes (NHS-/NH2-PSomes).

Synthetic polymersomes have structure similarity to bio-vesicles and could disassemble in response to stimuli for "on-demand" release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and in vivo. This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.

This paper highlights the potential benefits of using self-assembled polymeric nanoparticles of various shapes to enhance drug uptake. First, we highlight the growth and development of the polymersome, using a liposome as a blueprint for amphiphilic codelivery. Then, we focus on the advantages of nanoparticle elongation, drawing from the field of solid nanoparticles, as opposed to self-assembled vesicles which have not yet been extensively explored in shape-modulated drug delivery applications. Notably, regardless of the material used in the solid nanoparticle systems, more elongated shapes lead to greater cellular uptake, decreased interaction with the reticuloendothelial system macrophages, and increased circulation times. Finally, we highlight the methods currently being developed to modulate polymersome shape, thus providing a drug delivery system with the benefits derived from amphiphilicity and elongated structures. Current methods employed to modulate polymersome shape involve osmotic pressure gradients, solvent switching, and the use of cross-linking agents. Although these methods are successful in modulating polymersome shapes and the benefits of elongated nanoparticles in therapeutic targeting are clear, these methods have not yet been explored for applications in drug delivery.

An improved coarse-grained molecular dynamics model of magnetosensitive polymersome is presented. The modification allows facile constructing of the polymersome templates to be used in the simulations aimed at detailed description of the field-induced magnetodeformational behavior of these soft matter objects. The model is applied to study the magnetomechanical and structural responses of a spheroidal polymersome in magnetic field directed along and across the major axes of the spheroid. The results obtained reveal, in particular, a notable swelling effect caused by a uniform magnetic field.

The introduction of chirality into aqueous self-assemblies by employing isotactic block copolymers (BCPs) is an emerging field of interest as it promises special membrane properties of polymersomes not accessible by atactic BCPs. However, isotactic BCPs typically exhibit crystalline behaviour, inducing high membrane stiffness and limiting their applicability in systems involving membrane proteins or sensitive cargo. In this study, an isotactic yet fully amorphous BCP is introduced which overcomes these limitations. Three BCPs composed of poly(butylene oxide)-block-poly(glycidol) (PBO-b-PG), differing solely in their tacticities (R/S, R and S), were synthesised and characterised regarding their structural, optical and thermal properties. Their self-assembly into homogenous phases of nanoscopic polymersomes (referred to as small unilamellar vesicles, SUVs) was analysed, revealing stability differences between SUVs composed of the different BCPs. Additionally, microscopic giant unilamellar vesicles (GUVs) were prepared by double emulsion microfluidics. Only the atactic BCP formed GUVs which were stable over several hours, whereas GUVs composed of isotactic BCPs ruptured within several minutes after formation. The ability of atactic PBO-b-PG to form microreactors was elucidated by reconstituting the membrane protein OmpF in the GUV membrane by microfluidics and performing an enzyme reaction inside its lumen. The system presented here serves as platform to design versatile vesicles with flexible membranes composed of atactic or isotactic BCPs. Hence, they allow for the introduction of chirality into nano- or microreactors which is a yet unstudied field and could enable special biotechonological applications., Analysis of the membrane properties and stability of fully amorphous small and giant unilamellar vesicles composed of atactic or isotactic poly(butylene oxide)-block-poly(glycidol) (PBO-b-PG) amphiphilic diblock copolymers.

Owing to the increasing interest, the present review describes the advances in the self-assembly of amphiphilic as well as stimuli-responsive block copolymers. We briefly focus on the classification, synthesis process, and aqueous solution behavior of block copolymers. Advances in controlled radical polymerization in making tailor-made copolymers with different structures/types/monomers have enabled the fine-tuning of nanoscale aggregates to act as vehicles in controlled drug delivery systems. A transitory account on the formation, characterization, and features of the nanoscale micellar aggregates (polymer micelles, polymersomes, and polyelectrolyte complex micelles) in aqueous media is presented with various characterization approaches covering several schematic illustrations. This comprehensive review highlights the advances in stimuli-responsive double hydrophilic block copolymers in terms of their self-assembly and structural stability. We have also elaborated on the emerging case studies of the commercially available ethylene oxide–propylene oxide (EO–PO)-based block copolymeric surfactants from the viewpoint of their aqueous solution behavior and core–shell micelles for drug delivery applications combined with the discussion on the challenges and future perspectives of these amphiphiles.

Aqueous two-phase systems (ATPSs) have been widely used in the separation, purification, and enrichment of biomolecules for their excellent biocompatibility. While ultracentrifugation and microfluidic devices have been combined with ATPS to facilitate the separation of biomolecules and achieve high recovery yields, they often lack the ability to effectively isolate and separate biomolecules in low concentrations. In this work, we present a strategy that leverages the preferential partitioning of biomolecules in ATPS droplets to efficiently separate model extracellular vesicle (EV) particles. We demonstrate that the additional oil phase between the inner ATPS droplets and the aqueous continuous phase in triple emulsion droplets resolves the size controllability and instability issues of ATPS droplets, enabling the production of highly monodisperse ATPS-based polymersomes with enhanced stability for effective isolation of ATPS droplets from the surrounding environment. Furthermore, we achieve separation of model EV particles in a single dextran (DEX)-rich droplet by the massive production of ATPS-based polymersomes and osmotic-pressure-induced rupture of the selected polymersome in a hypertonic solution composed of poly(ethylene glycol) (PEG).

Antibiotic resistance is a serious global health problem necessitating new bactericidal approaches such as nanomedicines. Dendrimersomes (DSs) have recently become a valuable alternative nanocarrier to polymersomes and liposomes due to their molecular definition and synthetic versatility. Despite this, their biomedical application is still in its infancy. Inspired by the localized antimicrobial function of neutrophil phagosomes and the versatility of DSs, a simple three-component DS-based nanoreactor with broad-spectrum bactericidal activity is presented. This was achieved by encapsulation of glucose oxidase (GOX) and myeloperoxidase (MPO) within DSs (GOX-MPO-DSs), self-assembled from an amphiphilic Janus dendrimer, that possesses a semipermeable membrane. By external addition of glucose to GOX-MPO-DS, the production of hypochlorite (-OCl), a highly potent antimicrobial, by the enzymatic cascade was demonstrated. This cascade nanoreactor yielded a potent bactericidal effect against two important multidrug resistant pathogens, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), not observed for H2O2 producing nanoreactors, GOX-DS. The production of highly reactive species such as -OCl represents a harsh bactericidal approach that could also be cytotoxic to mammalian cells. This necessitates the development of strategies for activating -OCl production in a localized manner in response to a bacterial stimulus. One option of locally releasing sufficient amounts of substrate using a bacterial trigger (released toxins) was demonstrated with lipidic glucose-loaded giant unilamellar vesicles (GUVs), envisioning, e.g., implant surface modification with nanoreactors and GUVs for localized production of bactericidal agents in the presence of bacterial growth.

The equipping of nanoparticles with the peptide moiety recognizing a particular receptor, enables cell or tissue specific targeting, therefore the optimization of the targeted nanoparticles is a key factor in the formulation design process. In this paper, we report the optimization concept of Doxorubicin encapsulating PEtOx-b-PLA polymersome formulation equipped with Peptide18, which is a breast cancer recognizing tumor homing peptide, and the unveiling of the cell-specific delivery potential. The most dominant formulation parameters, which are the polymer to Doxorubicin mass ratio (w/w) and the aqueous to organic phase ratio (v/v), were optimized using Central Composite Design (CCD) based Response Surface Methodology. The characteristics of optimum polymersome formulation were determined as the hydrodynamic diameter of 146.35 nm, the PDI value of 0.136, and the encapsulation efficiency of 57.11% and TEM imaging, which are in agreement with the DLS data, showed the spherical morphology of the polymersomes. In order to demonstrate the breast cancer-specific delivery of targeted polymersomes, the flow cytometry and confocal microscopy analyses were carried out. The targeted polymersomes were accumulated 8 times higher in AU565 cells compared to MCF10A cells and the intracellular Doxorubicin was almost 10 times higher in AU565 cells. The CCD-mediated optimized targeted polymersomes proposed in this report holds the promise of targeted therapy for breast cancer and can be potentially used for the development of novel treatments. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213M760] Acknowledgements This research was financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK, 213M760) .

Polymersomes exhibit increased stability and reduced permeability compared to conventional lipid‐based compartments—making them an increasingly popular choice for the bottom‐up construction of synthetic cells. Here, the contraction and expansion of functionalized polymersome networks controlled by cholesterol‐tagged deoxyribonucleic acid (DNA) is demonstrated. Different types of block‐copolymer membranes are systematically screened to design a general framework for the self‐assembly of cholesterol‐tagged DNA into the polymersome membrane. Since the developed approach is DNA‐based, the individual symmetric and asymmetric functionalization of the inner and outer polymersome leaflets is possible, a feature which makes it unique in terms of anchoring flexibility and efficiency. In addition to the variety with regard to functionalization, the choice of DNA and temperature can also be used to manipulate the polymersome contact line and the polymersome bending energy. Overall, the strategy potentially allows for the unprecedented possibility to precisely control the contraction and expansion of polymersome network assembly.

Janus polymer vesicles (polymersomes) with biphasic membranes have special properties and potential applications in many fields. The big barrier for the preparation of Janus polymersomes lies in the difficulty of complete lateral microphase separation of polymers along the vesicle membrane due to the limited mobility. Herein, we present a systematic simulation study to provide a new strategy for the fabrication of Janus polymersomes based on water-in-oil-in-water double emulsions. Two incompatible block copolymers of AB and AC completely separate into two hemispheres of the polymersome driven by the dewetting of double emulsions, followed by the stabilization of the Janus structure with the block copolymers BC at the interface between AB and AC hemispheres. The simulation results demonstrate the formation of Janus polymersomes in a wide range of the incompatibility between blocks B and C. In addition, the morphologies of the Janus polymersomes can be readily regulated by changing the number of copolymers BC, the ratio of AB to AC, and the dewetting rate of organic solvents. Both the Janus and patchy polymersomes can be obtained through the adjustment of the dewetting rate. Besides, by introducing stimulus-cleavable copolymers of BC, the Janus polymersomes can perform controllable fission. Further comparison with similar experiments has also demonstrated the feasibility of our strategy. We believe the present work will be useful for the fabrication of polymersomes with controlled patches in a large quantity, and the stimulus-responsive fission process will also make the polymersomes promising in some applications like controlled drug delivery and cytomimetic membrane communication.

The self-assembly of amphiphilic diblock copolymers into polymeric vesicles, commonly known as polymersomes, results in a versatile system for a variety of applications including drug delivery and microreactors. In this study, we show that the incorporation of hydrophobic plasmonic nanoparticles within the polymersome membrane facilitates light-stimulated release of vesicle encapsulants. This work seeks to achieve tunable, triggered release with non-invasive, spatiotemporal control using single-pulse irradiation. Gold nanoparticles (AuNPs) are incorporated as photosensitizers into the hydrophobic membrane of micron-scale polymersomes and the cargo release profile is controlled by varying the pulse energy and nanoparticle concentration. We have demonstrated the ability to achieve immediate vesicle rupture as well as vesicle poration resulting in temporal cargo diffusion. Additionally, changing the pulse duration, from femtosecond to nanosecond, provides mechanistic insight into the photothermal and photomechanical contributors that govern membrane disruption in this polymer&ndash, nanoparticle hybrid system.

Combination of various polymeric blocks with distinct characteristics such as thermo-responsiveness, non-ionic nature and zwitterionic properties is an interesting approach toward fabricating copolymers undergoing a smart self-assembly process in an aqueous environment. In some cases, through a so-called "schizophrenic" self-assembly process, stimuli-induced self-assembly can occur from either double-hydrophilic or double hydrophobic polymers. In this process, the roles of the blocks forming the hydrophobic core and hydrophilic shell can be switched by changing the external conditions. This transformation in the solubilization profile leads to the fabrication of "smart" polymeric vehicles which could potentially control the release of their cargos as well as differentiate between encapsulated agents based on their charge and polarity properties. The aforementioned changes of the amphiphilicity of polymers in "schizophrenic" structures offer numerous self-assembly scenarios. In the current review, we summarize the polymer and peptide-based schizophrenic copolymers which could form micellar and vesicular (polymersome) systems providing novel structures with beneficial applications.

Capsules with holes in the walls exist in natural systems like virus capsids, and in biomimetic systems like immune-stimulating complexes vaccines and liposomes of phospholipids/surfactants mixtures. Structuring pores into stable membrane and controlling their opening are extremely useful for applications that require nano-pores as channels for material exchange and transportation. Polymersomes, which are stable and robust vesicles made of amphiphilic block copolymer, are good candidates for drug carriers or micro/nanoreactors. Engineering structure-inherent and light-gated nano-porous polymersomes is especially appealing, but still unexplored. Here we present these polymersomes made from a polymer including a tetraphenylethene (TPE) in its center. TPE is an emblematic fluorogen with aggregation-induced emission, which possesses two stereoisomers sensitive to photoisomerization. Trans-isomer of the polymer forms classical vesicles, cis-isomer forms cylindrical micelles, while trans/cis mixtures construct perforated vesicles with nano-pores. Under UV light, the classical polymersomes of trans-isomer can be perforated by its cis-counterpart generated from the photoisomerization.

Multicompartment polymeric nanocarriers which mimic the compartmentalized architecture of living cells have received considerable research attention in the biomedical field. The advancement of synthetic polymeric chemistry has allowed multicompartment polymeric nanocarriers to be tailored for biomedical applications such as drug delivery, encapsulated catalysis, and artificial cellular mimics. In this review, polymer-based multicompartment nanocarriers (multicompartment micelles, multicompartment polymersomes, and capsosomes) have been discussed. This review focuses on multicompartment systems applied to biomedical applications over the last ten years. The synthetic procedures and structural properties that impact the specific application are also highlighted.

Inspired by cell membrane structures, synthetic polymer vesicles caused great expectations for the preparation of biomedicine for decades. However, in contrast to bio-membranes, which consist of inhomogeneous features, conventional synthetic polymer vesicles usually consist of a homogeneous membrane which is purely made out of hydrophobic components. This significantly limited the versatility of synthetic polymer vesicle membranes. Fortunately, polymer vesicles with inhomogeneous membranes were recently developed to address this limitation. These new inhomogeneous membrane features introduced secondary functions to the vesicle membrane. Indeed, the membrane of polymer vesicles no longer only serves as a simple barrier that separates the interior from the exterior environment. Introduced membrane features can act as a versatile platform for tailorable nanoparticle functionalities, which allow functions such as biomacromolecule transportation, diabetes treatment, and cancer theranostics. This review highlights recent advances made with polymer vesicles with inhomogeneous membrane structures. More specifically, design principles, biomedical applications, and the future perspectives of such vesicles are summarized.