A facile and scalable method to synthesize PEGylated PDMAEMA for gene delivery.

In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non-viral transfection reagent, was used as a standard control. PEO-PDMAEMA-PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO-PDMAEMA-PEO could serve as a model to investigate more potential in the gene delivery area.

Dumbbell-Shaped, Block-Graft Copolymer with Aligned Domains for High-Performance Hydrocarbon Polymer Electrolyte Membranes.

Given the environmental concerns surrounding fluoromaterials, the use of high-cost perfluorinated sulfonic acids (PFSAs) in fuel cells and water electrolysis contradicts the pursuit of clean energy systems. Herein, we present a fluorine-free dumbbell-shaped block-graft copolymer, derived from the cost-effective triblock copolymer, poly(styrene-b-ethylene-co-butylene-b-styrene) (SEBS), for polymer electrolyte membranes (PEMs). This unique polymer shape led to the alignment of the hydrophobic-hydrophilic domains along a preferred orientation, resulting in the construction of interconnected proton channels across the membrane. A bicontinuous network allowed efficient proton transport with reduced tortuosity, leading to an exceptional ionic conductivity (249 mS cm-1 at 80 °C and 90 % relative humidity (RH)), despite a low ion exchange capacity (IEC; 1.41). Furthermore, membrane electrode assembly (MEA) prepared with our membrane exhibited stable performance over a period of 150 h at 80 °C and 30 % RH. This study demonstrates a novel polymer structure design and highlights a promising outlook for hydrocarbon PEMs as alternatives to PFSAs.

Solution-Phase Synthesis of KCl Nanocrystals Templated by PEO-PPO-PEO Triblock Copolymers Micelles.

The current work introduces the synthesis of inorganic salt nano/micro-crystals during the reduction of hydrogen tetrachloroaurate(III) by Pluronic triblock copolymers (P123, PEO20-PPO70-PEO20). The morphologies and component were confirmed using an electron microscope with an electronic differential system (EDS), and the crystal structures were determined with X-ray diffraction (XRD). The morphologies highly depend on the concentrations of Pluronic and pH values. The mean size of the nanocrystal and hollow micro-crystal were controlled typically in the range of 32-150 nm (side length) and 1.4 µm, respectively. Different from the electrospray-ionization (EI) method, a model in which KCl forms a supersaturated solution in the micellar core of Pluronic is used to explain the formation process. This work provides the new insight that inorganic salt nanocrystals could be synthesized with the template of micelles in pure aqueous solutions.

UV laser-processed microstructure for building biohybrid actuators with anisotropic movement.

Fabrication of a biohybrid actuator requires muscle cells anisotropically aligned in a line, curve, or combination of lines and curves (similar to the microstructure of living muscle tissue) to replicate lifelike movements, in addition to considering the arrangement of skeletal structure or muscular structure with anisotropic straight patterns. Here, we report a UV laser-processed microstructure for freely directing cellular alignment to engineer a biohybrid actuator composed of poly(styrene-block-butadiene-block-styrene triblock copolymer) (SBS) thin film with tailor-made microgrooves (MGs) and skeletal myotubes aligned along these MGs. Specifically, straight, circular, or curved MGs were transferred to SBS thin films from a UV laser-processed template, allowing for the successful alignment of myotubes along MGs. The biohybrid actuator, composed of anisotropically aligned myotubes on a curved microgrooved SBS thin film, was contracted by electrical stimulation. Contraction of biohybrid actuators with curved aligned myotubes permits twisted-like behavior, unlike straight microgrooved films. Therefore, the UV laser-ablation system is a unique maskless and rapid microfabrication technique that provides intriguing opportunities for omni-directional microgrooved structures to achieve the complex motion of living organisms.

Borate-containing triblock copolymer electrolytes for improved lithium-ion transference number and interface stability.

The electrolytes with high lithium-ion transference number (tLi+) can reduce the formation of concentration polarization during charge/discharge process and improve the electrochemical performance of lithium-ion batteries (LIBs). Herein, we report triblock copolymer electrolytes (PBOEE) containing borate. The sp2 hybridized boron atoms acting as Lewis acids can anchor the anions of lithium salts, enabling PBOEE to achieve high tLi+ of up to 0.53. Also, the borate groups can promote the formation of stable organic-rich solid electrolyte interphase (SEI) film, which enables the Li symmetric cell to cycle stably at 0.1 mA cm-2/0.1 mAh cm-2 for more than 3100 h with a low overpotential of 0.08 V under 50 °C. The optimized PBOEE_24 has an ionic conductivity of 1.41 × 10-4 S cm-1 and electrochemical stability window of 4.8 V vs. Li+/Li at 50 °C. Combining these advantages, the LiFePO4/PBOEE_24/Li cell exhibits an initial discharge specific capacity of 157.3 mA h g-1 at 0.5C with a capacity retention of 85 % after 600 cycles under 50 °C. At a higher current density of 1C, the discharge capacity maintains at 128.0 mA h g-1 after 400 cycles with a capacity retention of 84.88 %. These results suggest that block copolymer containing sp2 hybridized boron atoms is a promising all-solid-state polymer electrolyte.

Using Redox-Switchable Polymerization Catalysis to Synthesize a Chemically Recyclable Thermoplastic Elastomer.

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C. The triblock copolymers containing a higher percentage of THF versus CHO were more flexible, and a blend of triblock copolymers containing PLLA and poly(d-lactic acid) (PDLA) end-blocks resulted in a stereocomplex that further increased polymer flexibility. Besides the low cost of lactide and THF, the sustainability of this new class of triblock copolymers was also supported by their depolymerization, which was achieved by exposing the copolymers sequentially to FeCl3 and ZnCl2 /PEG under reactive distillation conditions.

Thermosensitive Triblock Copolymer for Slow-Release Lubricants under Ocular Conditions.

The ocular environment is crucial for a biological lubrication system. An unstable condition of tear film may cause a series of ocular diseases due to serious friction, such as dry eye syndrome, which has drawn extensive attention nowadays. In this study, an in vitro biocompatible superlubricity system, containing thermogelling copolymers (PCGA-PEG-PCGA) and slow-release lubricant (PEG 300/Tween 80), was constructed. First, the sol-gel transition temperature and gel strength of PCGA-PEG-PCGA were adjusted based on the ocular environment by regulating the length of PCGA blocks. Furthermore, the copolymer hydrogel exhibited a reliable slow-release property within 10 days and showed low cytotoxicity. Then, the superlubricity (coefficient of friction of approximately 0.005) was achieved with its released PEG 300/Tween 80 aqueous solution at the sliding velocity range of 1-100 mm s-1 and pressure range of 10-22 kPa. However, the lubrication behaviors varied, while PEG 300 chains and Tween 80 micelles were demonstrated to form a multilayer and a single layer adsorption structure on the sliding surface, respectively. On the whole, the composite lubrication systems, especially the one composed of Tween 80, showed excellent tribological properties owing to the stable slow-release and full hydration effects under ocular conditions, which hold great potential for improving ocular lubrication and maintaining human visual health.

Hybrid Shear-thinning Hydrogel Integrating Hyaluronic Acid with ROS-Responsive Nanoparticles.

Nanoparticle (NP) supra-assembly offers unique opportunities to tune macroscopic hydrogels' mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)-responsive NPs are physically crosslinked with hyaluronic acid (HA) through guest-host chemistry to create shear-thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)-bl-poly(N,N-dimethylacrylamide)-bl-poly(N,N-dimethylacrylamide-co-N-(1-adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self-assembled into NPs displaying adamantane on their corona. Self-assembled NPs are mixed with ß-cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA-only hydrogels, susceptibility to oxidative/enzymatic degradation, and inherent cell-protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self-assembled NPs significantly impacts hydrogel mechanical properties and shear-thinning behavior, while ROS-reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA-only hydrogels. This work provides insight into polymer structure-function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear-thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.

Synthesis and Characterization of ABA-Type Triblock Copolymers Using Novel Bifunctional PS, PMMA, and PCL Macroinitiators Bearing p-xylene-bis(2-mercaptoethyloxy) Core.

Syntheses of novel bifunctional poly(methyl methacrylate) (PMMA)-, poly(styrene) (PS)-, and (poly ε-caprolactone) (PCL)-based atom transfer radical polymerization (ATRP) macroinitiators derived from p-xylene-bis(1-hydroxy-3-thia-propanoloxy) core were carried out to obtain ABA-type block copolymers. Firstly, a novel bifunctional ATRP initiator, 1,4-phenylenebis(methylene-thioethane-2,1-diyl)bis(2-bromo-2-methylpropanoat) (PXTBR), synthesized the reaction of p-xylene-bis(1-hydroxy-3-thia-propane) (PXTOH) with α-bromoisobutryl bromide. The PMMA and PS macroinitiators were prepared by ATRP of methyl methacrylate (MMA) and styrene (S) as monomers using (PXTBR) as the initiator and copper(I) bromide/N,N,N',N″,N″-pentamethyldiethylenetriamine (CuBr/PMDETA) as a catalyst system. Secondly, di(α-bromoester) end-functionalized PCL-based ATRP macronitiator (PXTPCLBr) was prepared by esterification of hydroxyl end groups of PCL-diol (PXTPCLOH) synthesized by Sn(Oct)2-catalyzed ring opening polymerization (ROP) of ε-CL in bulk using (PXTOH) as initiator. Finally, ABA-type block copolymers, PXT(PS-b-PMMA-b-PS), PXT(PMMA-b-PS-b-PMMA), PXT(PS-b-PCL-b-PS), and PXT(PMMA-b-PCL-b-PMMA), were synthesized by ATRP of MMA and S as monomers using PMMA-, PS-, and PCL-based macroinitiators in the presence of CuBr/PMDETA as the catalyst system in toluene or N,N-dimethylformamide (DMF) at different temperatures. In addition, the extraction abilities of PCL and PS were investigated under liquid-liquid phase conditions using heavy metal picrates (Ag+, Cd2+, Cu2+, Hg2+, Pb2+, and Zn2+) as substrates and measuring with UV-Vis the amounts of picrate in the 1,2-dichloroethane phase before and after treatment with the polymers. The extraction affinity of PXTPCL and PXTPS for Hg2+ was found to be highest in the liquid-liquid phase extraction experiments. Characterizations of the molecular structures for synthesized novel initiators, macroinitiators, and the block copolymers were made by spectroscopic (FT-IR, ESI-MS, 1H NMR, 13C NMR), DSC, TGA, chromatographic (GPC), and morphologic SEM.

Synthesis and Comparative Study of Polyether-b-polybutadiene-b-polyether Triblock Copolymers for Use as Polyurethanes.

In this paper, the effects of HTPBs with different main-chain microstructures on their triblock copolymers and polyurethane properties were investigated. Three polyether-modified HTPB triblock copolymers were successfully synthesized via a cationic ring-opening copolymerization reaction using three HTPBs with different microstructures prepared via three different polymerization methods as the macromolecular chain transfer agents and tetrahydrofuran (THF) and propylene oxide (PO) as the copolymerization monomers. Finally, the corresponding polyurethane elastomers were prepared using the three triblock copolymers as soft segments and toluene diisocyanate (TDI) as hard segments. The results of an analysis of the triblock copolymers showed that the triblock copolymers had lower viscosity and glass transition temperature (Tg) values as the HTPB 1,2 structure content decreased, although the effect on the thermal decomposition temperature was not significant. An analysis of the polyurethane elastomers revealed that as the content of the 1,2 structure in HTPB increased, its corresponding polyurethane elastomers showed a gradual increase in breaking strength and a gradual decrease in elongation at break. In addition, PU-1 had stronger crystallization properties compared to PU-2 and PU-3. However, the differences in the microstructures of the HTPBs did not seem to have much effect on the surface properties of the polyurethane elastomers.

Recent advances of Pluronic-based copolymers functionalization in biomedical applications.

The design of polymeric biocompatible nanomaterials for biological and medical applications has received special attention in recent years. Among different polymers, the triblock type copolymers (EO)x(PO)y(EO)x or Pluronics® stand out due its favorable characteristics such as biocompatibility, low tissue adhesion, thermosensitivity, and structural capacity to produce different types of macro and nanostructures, e.g. micelles, vesicles, nanocapsules, nanospheres, and hydrogels. However, Pluronic itself is not the "magic bullet" and its functionalization via chemical synthesis following biologically oriented design rules is usually required aiming to improve its properties. Therefore, this paper presents some of the main publications on new methodologies for synthetic modifications and applications of Pluronic-based nanoconstructs in the biomedical field in the last 15 years. In general, the polymer modifications aim to improve physical-chemical properties related to the micellization process or physical entrapment of drug cargo, responsive stimuli, active targeting, thermosensitivity, gelling ability, and hydrogel formation. Among these applications, it can be highlighted the treatment of malignant neoplasms, infectious diseases, wound healing, cellular regeneration, and tissue engineering. Functionalized Pluronic has also been used for various purposes, including medical diagnosis, medical imaging, and even miniaturization, such as the creation of lab-on-a-chip devices. In this context, this review discusses the main scientific contributions to the designing, optimization, and improvement of covalently functionalized Pluronics aiming at new strategies focused on the multiple areas of the biomedical field.

Lyotropic liquid crystal elastomers for drug delivery.

Silicone elastomers like polydimethylsiloxane (PDMS) possess a combination of attractive material and biological properties motivating their widespread use in biomedical applications. Development of elastomers with capacity to deliver active therapeutic substances in the form of drugs is of particular interest to produce medical devices with added functionality. In this work, silicone-based lyotropic liquid crystal elastomers with drug-eluting functionality were developed using PDMS and triblock copolymer (diacrylated Pluronic F127, DA-F127). Various ternary PDMS-DA-F127-H2O compositions were explored and evaluated. Three compositions were found to have specific properties of interest and were further investigated for their nanostructure, mechanical properties, water retention capacity, and morphology. The ability of the elastomers to encapsulate and release polar and nonpolar substances was demonstrated using vancomycin and ibuprofen as model drugs. It was shown that the materials could deliver both types of drugs with a sustained release profile for up to 6 and 5 days for vancomycin and ibuprofen, respectively. This works demonstrates a lyotropic liquid crystal, silicone-based elastomer with tailorable mechanical properties, water retention capacity and ability to host and release polar and nonpolar active substances.

Triblock copolymer-grafted restricted access materials with zwitterionic polymer outer layers for highly efficient extraction of fluoroquinolones and exclusion of proteins.

High-selectivity and high-exclusion restricted access materials (RAMs) benefit the analysis of biological samples. Herein, triblock copolymer-functionalized poly(4-vinylbenzyl chloride-co-divinylbenzene) (PVBC/DVB) microspheres were prepared via the sequential surface-initiated atom radical polymerization of hydrophobic styrene (St), ionic vinylimidazole (VIm), and zwitterionic sulfobetaine methacrylate (SBMA), affording RAMs with multiple interaction-adsorption sites and zwitterionic polymer exclusion sites on the internal and external surfaces of PVBC/DVB. The preferential extraction of fluoroquinolones (FQs) is realized based on the hydrophobic/π-π/ion exchange interactions due to the grafted poly-St-VIm, and the zwitterionic poly-SBMA block in the triblock copolymers can efficiently exclude various proteins. A sensitive detection method for FQs in chicken was established by solid phase extraction with RAMs as adsorbent combined with UPLC-MS/MS, achieving wide linearity (2.0-200.0 ng mL-1), low limit of detection (0.5 µg kg-1) and limit of quantification (1.5 µg kg-1), and good inter- and intraday precision with satisfactory recoveries (104.1%-117.7% and 115.3%-121.2% with RSDs < 12%).

Strong and Tough Nanostructured Hydrogels and Organogels Prepared by Polymerization-Induced Self-Assembly.

In nature, the hierarchical structure of biological tissues endows them with outstanding mechanics and elaborated functions. However, it remains a great challenge to construct biomimetic hydrogels with well-defined nanostructures and good mechanical properties. Herein, polymerization-induced self-assembly (PISA) is for the first time exploited as a general strategy for nanostructured hydrogels and organogels with tailored nanodomains and outstanding mechanical properties. As a proof-of-concept, PISA of BAB triblock copolymer is used to fabricate hydrogels with precisely regulated spherical nanodomains. These nanostructured hydrogels are strong, tough, stretchable, and recoverable, with mechanical properties correlating to their nanostructure. The outstanding mechanical properties are ascribed to the unique network architecture, where the entanglements of the hydrophilic chains act as slip links that transmit the tension to the micellar crosslinkers, while the micellar crosslinkers dissipate the energy via reversible deformation and irreversible detachment of the constituting polymers. The general feasibility of the PISA strategy toward nanostructured gels is confirmed by the successful fabrication of nanostructured hydrogels, alcogels, poly(ethylene glycol) gels, and ionogels with various PISA formulations. This work has provided a general platform for the design and fabrication of biomimetic hydrogels and organogels with tailorable nanostructures and mechanics and will inspire the design of functional nanostructured gels.

Dynamic Light Scattering Based Microrheology of End-Functionalised Triblock Copolymer Solutions.

Nano-sized particles functionalised with short single-stranded (ss)DNAs can act as detectors of complementary DNA strands. Here we consider tri-block-copolymer-based, self-assembling DNA-coated nanoparticles. The copolymers are chemically linked to the DNA strands via azide (N3) groups. The micelles aggregate when they are linked with complementary ssDNA. The advantage of such block-copolymer-based systems is that they are easy to make. Here we show that DNA functionalisation results in inter-micellar attraction, but that N3-groups that have not reacted with the DNA detector strands also change the phase behaviour of the tri-block polymer solution. We studied the triblock copolymer, Pluronic® F108, which forms spherical micelles in aqueous solutions upon heating. We find that the triblock chains ending with either an N3 or N3-DNA complex show a dramatic change in phase behaviour. In particular, the N3-functionalisation causes the chain ends to cluster below the critical micelle temperature (CMT) of pure F108, forming flower-micelles with the N3-groups at the core, while the PPO groups are exposed to the solvent. Above the CMT, we see an inversion with the PPO chains forming the micellar core, while the N3-groups are now aggregating on the periphery, inducing an attraction between the micelles. Our results demonstrate that, due to the two competing self-assembling mechanisms, the system can form transient hydrogels.

Hybrid Poly(ß-amino ester) Triblock Copolymers Utilizing a RAFT Polymerization Grafting-From Methodology.

The biocompatibility, biodegradability, and responsiveness of poly(ß-amino esters) (PBAEs) has led to their widespread use as biomaterials for drug and gene delivery. Nonetheless, the step-growth polymerization mechanism that yields PBAEs limits the scope for their structural optimization toward specific applications because of limited monomer choice and end-group modifications. Moreover, to date the post-synthetic functionalization of PBAEs has relied on grafting-to approaches, challenged by the need for efficient polymer-polymer coupling and potentially difficult post-conjugation purification. Here a novel grafting-from approach to grow reversible addition-fragmentation chain transfer (RAFT) polymers from a PBAE scaffold is described. This is achieved through PBAE conversion into a macromolecular chain transfer agent through a multistep capping procedure, followed by RAFT polymerization with a range of monomers to produce PBAE-RAFT hybrid triblock copolymers. Following successful synthesis, the potential biological applications of these ABA triblock copolymers are illustrated through assembly into polymeric micelles and encapsulation of a model hydrophobic drug, followed by successful nanoparticle (NP) uptake in breast cancer cells. The findings demonstrate this novel synthetic methodology can expand the scope of PBAEs as biomaterials.

Rational Design of a Robust Flexible Triblock Polyurea Copolymer Protective Layer for High-Performance Lithium Metal Batteries.

Dendrite growth and volume expansion in lithium metal are the most important obstacles affecting the actual applications of lithium metal batteries. Herein, we design a robust flexible artificial solid electrolyte interphase layer based on a triblock copolymer polyurea film, which promotes uniform lithium deposition on the surface of the lithium metal electrode and has a high lithium-ion transference number. The high elasticity and close contact of polyurea compounds effectively suppress lithium dendrite growth and volume expansion in the Li anode, which are effectively confirmed by electrochemical characterization and optical microscopy observation. The symmetrical batteries with the PU-Li metal anode can achieve stable and reversible Li plating/stripping over 500 h at a current density of 5 mA cm-2. Matched with the high-mass-loaded S cathode and the commercial NCM523 cathode, this film significantly improves the cycle life of lithium metal batteries.

Influence of Block Ratio on Thermal, Optical, and Photovoltaic Properties of Poly(3-hexylthiophene)-b-poly(3-butylthiophene)-b-poly(3-octylthiophene).

Efforts to improve the solar power conversion efficiencies of binary bulk heterojunction-type organic photovoltaic devices using an active layer consisting of a poly-(3-alkylthiophene) (P3AT) homopolymer and a suitable fullerene derivative face barriers caused by the intrinsic properties of homopolymers. To overcome such barriers, researchers might be able to chemically tailor homopolymers by means of monomer ratio-balanced block copolymerization to obtain preferable properties. Triblock copolymers consisting of three components-3-hexylthiophene (HT), 3-butylthiophene (BT), and 3-octylthiophene (OT)-were synthesized via Grignard metathesis (GRIM) polymerization. The component ratios of the synthesized block copolymers were virtually the same as the feeding ratios of the monomers, a fact which was verified using 1H-NMR spectra. All the copolymers exhibited comparable crystalline and melting temperatures, which increased when one type of monomer became dominant. In addition, their power conversion efficiencies and photoluminescence properties were governed by the major components of the copolymers. Interestingly, the HT component-dominated block copolymer indicated the highest power conversion efficiency, comparable to that of its homopolymer, although its molecular weight was significantly shorter.

3D Printing of Triamcinolone Acetonide in Triblock Copolymers of Styrene-Isobutylene-Styrene as a Slow-Release System.

Additive manufacturing has a wide range of applications and has opened up new methods of drug formulation, in turn achieving attention in medicine. We prepared styrene-isobutylene-styrene triblock copolymers (SIBS; Mn = 10 kDa-25 kDa, PDI 1,3-1,6) as a drug carrier for triamcinolone acetonide (TA), further processed by fused deposition modeling to create a solid drug release system displaying improved bioavailability and applicability. Living carbocationic polymerization was used to exert control over block length and polymeric architecture. Thermorheological properties of the SIBS polymer (22.3 kDa, 38 wt % S) were adjusted to the printability of SIBS/TA mixtures (1-5% of TA), generating an effective release system effective for more than 60 days. Continuous drug release and morphological investigations were conducted to probe the influence of the 3D printing process on the drug release, enabling 3D printing as a formulation method for a slow-release system of Triamcinolone.

Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems.

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.