Dually Gated Polymersomes for Gene Delivery.

An ideal gene carrier requires an excellent gating system to efficiently load, protect, deliver, and release environmentally sensitive nucleic acids on demand. Presented in this communication is a polymersome with a "boarding gate" and a "debarkation gate" in the membrane to complete the above important missions. This dually gated polymersome is self-assembled from a block copolymer, poly(ethylene oxide)- block-poly[ N-isopropylacrylamide- stat-7-(2-methacryloyloxyethoxy)-4-methylcoumarin- stat-2-(diethylamino)ethyl methacrylate] [PEO- b-P(NIPAM- stat-CMA- stat-DEA)]. The hydrophilic PEO chains form the coronas of the polymersome, whereas the temperature and pH-sensitive P(NIPAM- stat-CMA- stat-DEA) block forms the dually gated heterogeneous membrane. The temperature-controlled "boarding gate" can be opened at room temperature for facile encapsulation of siRNA and plasmid DNA into polymersomes directly in aqueous solution. The "debarkation gate" can be triggered by proton sponge effect for intracellular release. Biological studies confirmed the successful encapsulation of siRNA and plasmid DNA, efficient in vitro and in vivo gene transfection, and the expression of green fluorescent protein (GFP) from GFP-encoding plasmid, suggesting that this kind of polymersome with a dual gating system can serve as an excellent biomacromolecular shuttle for gene delivery and other biological applications.

Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating Copolymers for Bone Repair.

It is an important challenge for bone repair to effectively deliver growth factors and at the same time to prevent and cure inflammation without obvious pathogen resistance. We designed a kind of antibacterial peptide-mimetic alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the PMACs against E. coli and S. aureus are 8.0 µg/mL, which are much lower than that of antibacterial peptides synthesized by other methods such as widely used ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can self-assemble into polymer vesicles (polymersomes) in pure water with low cytotoxicity (IC50 > 1000 µg/mL), which can encapsulate growth factors in aqueous solution and release them during long-term antibacterial process for facilitating bone repair. We also find that the alternating structure is essential for the excellent antibacterial activity. The in vivo tests in rabbits confirmed that the growth-factor-encapsulated antibacterial vesicles have better bone repair ability compared with control groups without antibacterial vesicles. Overall, we have provided a novel method for designing PMAC-based highly effective intrinsically antibacterial vesicles that may have promising biomedical applications in the future.

Synthesis and Mechanism Insight of a Peptide-Grafted Hyperbranched Polymer Nanosheet with Weak Positive Charges but Excellent Intrinsically Antibacterial Efficacy.

Antimicrobial resistance is an increasingly problematic issue in the world and there is a present and urgent need to develop new antimicrobial therapies without drug resistance. Antibacterial polymers are less susceptible to drug resistance but they are prone to inducing serious side effects due to high positive charge. Herein we report a peptide-grafted hyperbranched polymer which can self-assemble into unusual nanosheets with highly effective intrinsically antibacterial activity but weak positive charges (+ 6.1 mV). The hyperbranched polymer was synthesized by sequential Michael addition-based thiol-ene and free radical mediated thiol-ene reactions, and followed by ring-opening polymerization of N-carboxyanhydrides (NCAs). The nanosheet structure was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) studies. Furthermore, a novel "wrapping and penetrating" antibacterial mechanism of the nanosheets was revealed by TEM and it is the key to significantly decrease the positive charges but have a very low minimum inhibitory concentration (MIC) of 16 µg mL(-1) against typical Gram-positive and Gram-negative bacteria. Overall, our synthetic strategy demonstrates a new insight for synthesizing antibacterial nanomaterials with weak positive charges. Moreover, the unique antibacterial mechanism of our nanosheets may be extended for designing next-generation antibacterial agents without drug resistance.

Giant Polymer Vesicles with a Latticelike Membrane.

Hierarchical self-assembly offers great possibilities to mimic biological systems with finely arranged complex structures. Herein, we demonstrate the preparation and formation mechanism of an unusual giant polymer vesicle with a latticelike membrane (GVLM). This GVLM is formed by fusion-induced particle assembly (FIPA) of small vesicles that are self-assembled from poly(ethylene oxide)-block-poly[(2-(tetrahydrofuranyloxy)ethyl methacrylate)-stat-(6-(3,3-diphenylnaphthopyranyloxy)hexyl methacrylate)] [PEO43-b-P(TMA22-stat-NMA4)]. Flexible TMA units with high chain mobility and relatively rigid NMA units with intrinsic π-π stacking form the hydrophobic block. These units act as "antifusion" and "profusion" components, respectively. The latticelike membrane of the final GVLM consists of hundreds of small polymer vesicles that are interconnected via multiple interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies show that the diameter of the GVLMs is 800-1000 nm. Overall, we provide a new insight into the judicious preparation of hierarchical nanostructures via chemical synthesis and FIPA.

Polymer Vesicles: Modular Platforms for Cancer Theranostics.

As an emerging field that is receiving an increasing amount of interest, theranostics is becoming increasingly important in the field of nanomedicine. Among the various smart platforms that have been proposed for use in theranostics, polymer vesicles (or polymersomes) are among the most promising candidates for integration of designated functionalities and modalities. Here, a brief summary of typical theranostic platforms is presented with a focus on modular polymer vesicles. To highlight modularity, the different methodologies for designing therapeutic and diagnostic modules are classified and current examples of theranostic vesicles that excel in both performance and design principle are provided. Finally, future prospects for theranostic polymer vesicles that can be readily prepared with functional modules are proposed. Overall, theranostic polymer vesicles with modular modalities and functions are more promising in nanomedicine than simply being "over-engineered".

Disclosing the nature of thermo-responsiveness of poly(N-isopropyl acrylamide)-based polymeric micelles: aggregation or fusion?

The apparent size increase of poly(N-isopropyl acrylamide) (PNIPAM)-based polymeric micelles upon heating was usually ascribed to their volume growth or aggregation in aqueous solution. Herein we designed a photo-cross-linkable PNIPAM-based copolymer and proposed another thermo-responsive behaviour - fusion, which is disclosed by transmission electron microscopy (TEM) after in situ fixing morphologies at desired temperatures.

Preparation and mechanism insight of nuclear envelope-like polymer vesicles for facile loading of biomacromolecules and enhanced biocatalytic activity.

The facile loading of sensitive and fragile biomacromolecules, such as glucose oxidase, hemoglobin, and ribonucleic acid (RNA), via synthetic vehicles directly in pure aqueous media is an important technical challenge. Inspired by the nucleus pore complex that connects the cell nucleus and the cytoplasm across the nuclear envelope, here we describe the development of a kind of polymeric nuclear envelope-like vesicle (NEV) to address this problem. The NEV is tailored to form the polymer pore complex (70 nm, similar to a nucleus pore complex) within the vesicle membrane based on nanophase segregation, which is confirmed via fluorescence spectrometry and dynamic light scattering (DLS) during self-assembly. This pH-triggered polymer pore complex can mediate the transportation of biomacromolecules across the vesicle membrane. Moreover, the NEVs facilitate the natural consecutive enzyme-catalyzed reactions via the H(+) sponge effect. This simple strategy might also be extended for mimicking other synthetic cell organelles.

Antibacterial polymeric nanostructures for biomedical applications.

The high incidence of bacterial infection and the growing resistance of bacteria to conventional antibiotics have resulted in the strong need for the development of new generation of antibiotics. Nano-sized particles have been considered as novel antibacterial agents with high surface area and high reactivity. The overall antibacterial properties of antimicrobial nanostructures can be significantly enhanced compared with conventional antibacterial agents not in a regular nanostructure, showing a better effect in inhibiting the growth and reproduction of microbials such as bacteria and fungi, etc. In this review, recent advances in the research and applications of antimicrobial polymeric nanostructures have been highlighted, including silver-decorated polymer micelles and vesicles, antimicrobial polymer micelles and vesicles, and antimicrobial peptide-based vesicles, etc. Furthermore, we proposed the current challenges and future research directions in the field of antibacterial polymeric nanostructures for the real-world biomedical applications.

A multifunctional azobenzene-based polymeric adsorbent for effective water remediation.

The efficient removal of trace carcinogenic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs) and ionic dyes, from water is an important technical challenge. We report a highly effective recyclable multifunctional azobenzene (AZ)-based silica-supported polymeric adsorbent which can simultaneously remove both PAHs and anionic dyes from water to below parts per billion (ppb) level based on multiple interactions such as the hydrophobic effect, π-π stacking and electrostatic interactions, thus providing a new strategy for designer water remediation materials.

Preparation of novel magnetic hollow mesoporous silica microspheres and their efficient adsorption.

Magnetic hollow mesoporous silica microspheres (MHMSs) were successfully prepared by employing yolk-shell magnetic silica spheres as the template together with the coating of tetraethoxysilane (TEOS)/hexadecyl trimethoxysilane (C(16)TMS) hybrid. The microstructure and properties of MHMSs were studied by TEM, SEM, XRD, BET, and VSM characterizations. The average diameter of MHMSs was about 300 nm and the mesoporous shell thickness was totally around 70 nm. The 11 nm magnetite nanoparticles were homogeneously embedded in the mesoporous silica shell. Meanwhile, the adsorption and separation process of Rhodamine B were carried out to demonstrate that the material could be used for the adsorbent.

Facile one-pot synthesis of yolk-shell superparamagnetic nanocomposites via ternary phase separations.

Yolk-shell composites with an Fe(3)O(4)/silica hybrid shell and a polymer core are prepared via a facile one-pot and self-template process. Thicknesses of the inorganic shell and interior space of the composites are well controlled by tuning the ternary phase separations.