Membrane-Bound Inward-Growth of Artificial Cytoskeletons and Their Selective Disassembly.

The cytoskeleton is one of the most important cellular components. Up to now, most of the reported artificial cytoskeletons are based on a gel-in-vesicle strategy. Herein, we report a membrane-bound inward-growth pathway to prepare cytoskeleton-like and radially aligned nanofibers grown from capsule membranes to get membrane-bound artificial cytoskeletons (MACs). The mechanism therein is disclosed through the direct observation of the intermediates in both dried and liquid states. Furthermore, the as-prepared MACs show a selective disassembly behavior in the presence of reductants: both capsule membranes and MACs can be disassembled or only MACs can be disassembled through the selective introduction of dynamic disulfide bonds (DS) into them and by the switch of ultraviolet (UV) irradiation. The present work provides a new hierarchical self-assembly way to construct artificial cytoskeletons with controlled compositions and orientations.

Mussel-Inspired Alternating Copolymer as a High-Performance Adhesive Material Both at Dry and Under-Seawater Conditions.

Marine mussels have the ability to cling to various surfaces at wet or underwater conditions, which inspires the research of catechol-functionalized polymers (CFPs) to develop high-performance adhesive materials. However, these polymeric adhesives generally face the problems of complex synthetic route, and it is still high challenging to prepare CFPs with excellent adhesive performance both at dry and underwater conditions. Herein, a mussel-inspired alternating copolymer, poly(dopamine-alt-2,2-bis(4-glycidyloxyphenyl)propane) (P(DA-a-BGOP)), is synthesized in one step by using commercially available monomers through epoxy-amino click chemistry. The incorporation of polar groups and rigid bisphenol A structures into the polymer backbone enhances the cohesion energy of polymer matrix. The alternating polymer structure endows the polymers with high catechol content and controlled polymer sequence. As a result, P(DA-a-BGOP) exhibits a strong bonding strength as high as 16.39 ± 2.13 MPa on stainless steel substrates after a hot pressing procedure and displays a bonding strength of 1.05 ± 0.05 MPa on glass substrates at an under-seawater condition, which surpasses most commercial adhesives.

Hyperbranched Multiarm Copolymers with a UCST Phase Transition: Topological Effect and the Mechanism.

A novel thermoresponsive hyperbranched multiarm copolymer with a hydrophobic hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] core and many poly(acrylamide- co-acrylonitrile) (P(AAm- co-AN)) arms was for the first time synthesized through a reversible addition-fragmentation chain-transfer polymerization. These copolymers show reversible, sharp, and controlled temperature-responsive phase transitions at the upper critical solution temperature (UCST) in water and electrolyte solution. It is the first report on the hyperbranched copolymers with a UCST transition. Two series copolymers with variable AN content (series A) and variable arm length (series B) were synthesized to study the influence of molecular structure on the UCST transition. It was found that the UCST of copolymers could be raised by increasing the AN content or decreasing the arm length. Most interestingly, the amplification effect of the hyperbranched topological structure leads to a broad change of the UCST from 33.2 to 65.2 °C with the little change of AN content (5.9%). On the basis of variable temperature nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy, a UCST transition mechanism, in combination with hydrophilic/hydrophobic balance and multimicelle aggregate (MMA), was proposed. This work enriches the UCST copolymer topology and may extend the knowledge on the structure-activity relationship as well as the mechanism of the UCST polymers.

Construction of Light-Harvesting Polymeric Vesicles in Aqueous Solution with Spatially Separated Donors and Acceptors.

This communication describes polymer vesicles self-assembled from hyperbranched polymers (branched polymersomes (BPs)) as scaffolds, conceptually mimicking the natural light-harvesting system in aqueous solution. The system is constructed with hydrophobic 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) as donors encapsulated in the hydrophobic hyperbranched cores of the vesicles and the hydrophilic Rhodamine B (RB) as acceptors incorporated on the surface of the vesicles through the cyclodextrin (CD)/RB host-guest interactions, through which the donors and acceptors are spatially separated to effectively avoid the self-quenching between donors. This vesicular light harvesting system has presented good energy transfer efficiency of about 80% in water, and can be used as the ink to write multiclolor letters. In addition, due to the giant dimension of BPs, the real-time fluorescent images of the vesicles under an optical microscope can be observed to prove the light-harvesting process. It is supposed that such a vesicular light-harvesting antenna can be used to construct artificial photosynthesis systems in the future.

An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy.

Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are the most clinically advanced but they require cumbersome four components and suffer from inflammation-related side effects that should be minimized for safety. Yet, a certain level of proinflammatory responses and innate immune activation are required to evoke T-cell immunity for mRNA cancer vaccination. To address these issues and develop potent yet low-inflammatory mRNA cancer vaccine vectors, a series of alternating copolymers "PHTA" featured with ortho-hydroxy tertiary amine (HTA) repeating units for mRNA delivery is synthesized, which can play triple roles of condensing mRNA, enhancing the polymeric nanoparticle (PNP) stability, and prolonging circulation time. Unlike LNPs exhibiting high levels of inflammation, the PHTA-based PNPs show negligible inflammatory side effects in vivo. Importantly, the top candidate PHTA-C18 enables successful mRNA cancer vaccine delivery in vivo and leads to a robust CD8+ T cell mediated antitumor cellular immunity. Such PHTA-based integrated PNP provides a potential approach for establishing mRNA cancer vaccines with good inflammatory safety profiles.

Asymmetric Vesicles Self-Assembled by Amphiphilic Sequence-Controlled Polymers.

The asymmetric distribution of lipids on the inner and outer membranes of a cell plays a pivotal role in the physiological and immunological activities of life. It has inspired the elaboration of synthetic asymmetric vesicles for the discovery of advanced materials and functions. The asymmetric vesicles were generally prepared by amphiphilic block copolymers. We herein report on the formation of asymmetric vesicles self-assembled by amphiphilic sequence-controlled polymers with two hydrophilic segments SU and TEO. We also developed an efficient fluorescence titration method with europium(III) ions (Eu3+) to determine the uneven distribution of SU and TEO. SU units are preferentially located on the outer membrane and TEO on the inner membrane of the resulting vesicles, which is facilitated by the electrostatic repulsion of SU and the U-shaped folding of the hydrophobic backbone of the resulting polymers. This work shows that sequence-controlled polymers with alternating monomer sequence provide a powerful toolbox for the elaboration of important yet challenging self-assembled structures for emerging functions and properties.

Porphyrin Alternating Copolymer Vesicles for Photothermal Drug-Resistant Bacterial Ablation and Wound Disinfection.

In the past two decades, polymer vesicles have aroused widespread interest and made significant developments. However, the applications of polymer vesicles in anti-infective therapy are still limited. Here, we construct a polymer vesicle (TPPBV) from a porphyrin alternating copolymer P(TPP-a-BDE) with a high photothermal conversion efficiency (54.1%), which is attributed to the unique chain-folding mechanisms of the alternating copolymer. In particular, TPPBVs exhibit great photothermal antibacterial activity against both Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative extended-spectrum ß-lactamases Escherichia coli (ESBL E. coli). Moreover, TPPBVs present a specific antibiofilm effect, and they also have remarkable therapeutic effects in vivo on an MRSA-infected mice model. We believe that the porphyrin alternating copolymer vesicles for photothermal bacterial ablation reported here will extend the applications of polymer vesicles.

In situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy.

Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have seldom been used as PTAs due to the unsatisfactory photothermal conversion efficiency resulting from the irregular packing of chromophores in the vesicle membranes. Here we report a nano-sized polymer vesicle from hyperbranched polyporphyrins with favorable photothermal stability and extraordinarily high photothermal efficiency (44.1%), showing great potential in imaging-guided PTT for tumors through in vitro and in vivo experiments. These excellent properties are attributed to the in situ supramolecular polymerization of porphyrin units inside the vesicle membrane into well-organized 1D monofilaments driven by π-π stacking. We believe the supramolecular polymerization-enhanced self-assembly process reported here will shed a new light on the design of supramolecular materials with new structures and functions.

Facile Synthesis of a H2O2-Responsive Alternating Copolymer Bearing Thioether Side Groups for Drug Delivery and Controlled Release.

A novel amphiphilic alternating copolymer with thioether side groups (P(MSPA-a-EG)) was synthesized through an amine-epoxy click reaction of 3-(methylthio)propylamine (MSPA) and ethylene glycol diglycidyl ether. P(MSPA-a-EG) was characterized in detail by nuclear magnetic resonance (NMR), gel permeation chromatography, Fourier transformed infrared, differential scanning calorimeter, and thermogravimetric analysis to confirm the successful synthesis. Due to its amphiphilic structure, P(MSPA-a-EG) could self-assemble into spherical micelles with an average diameter of about 151 nm. As triggered by H2O2, theses micelles could disassemble because hydrophobic thioether groups are transformed to hydrophilic sulfoxide groups in MSPA units. The oxidant disassemble process of micelles was systemically studied by dynamic light scattering, transmission electron microscopy, and 1H NMR measurements. The MTT assay against NIH/3T3 cells indicated that P(MSPA-a-EG) micelles exhibited good biocompatibility. Furthermore, they could be used as smart drug carriers to encapsulate hydrophobic anticancer drug doxorubicin (DOX) with 4.90% drug loading content and 9.81% drug loading efficiency. In vitro evaluation results indicated that the loaded DOX could be released rapidly, triggered by H2O2. Therefore, such a novel alternating copolymer was expected to be promising candidates for controlled drug delivery and release.