Synthesis of Metallopolymers and Direct Visualization of the Single Polymer Chain.

During the past few decades, the study of the single polymer chain has attracted considerable attention with the goal of exploring the structure-property relationship of polymers. It still, however, remains challenging due to the variability and low atomic resolution of the amorphous single polymer chain. Here, we demonstrated a new strategy to visualize the single metallopolymer chain with a hexameric or trimeric supramolecule as a repeat unit, in which Ru(II) with strong coordination and Fe(II) with weak coordination were combined together in a stepwise manner. With the help of ultrahigh-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM) and scanning tunneling spectroscopy (STS), we were able to directly visualize both Ru(II) and Fe(II), which act as staining reagents on the repeat units, thus providing detailed structural information for the single polymer chain. As such, the direct visualization of the single random polymer chain is realized to enhance the characterization of polymers at the single-molecule level.

Investigating the effect of mono- and multivalent counterions on the conformation of poly(styrenesulfonic acid) by nanopores.

Polyelectrolytes are useful materials that have many technical, medical, physiological and biological applications. The properties of polyelectrolytes are determined not only by their chemical composition but also by their conformational states. However, the conformations of polyelectrolytes in solution are very difficult to characterize. Herein, we propose to use a protein nanopore to investigate the effect of mono- and multivalent counterions on the conformational changes of a simple polyelectrolyte, sodium poly(styrenesulfonic acid) (NaPSS). High concentration of KCl induced a conformational transition of NaPSS from "swollen random coil" form in low salt concentration to "random coil" form and was evidenced by the changes of the translocation event pattern. Addition of Mg2+ in buffer solution did not cause notable changes of NaPSS translocation events, but Dy3+ and Y3+ were shown to have remarkable effects on the translocation profile of NaPSS. Bridging events caused by Dy3+ or Y3+ between polyelectrolyte chains largely affected current blockage and dwell time of the translocation events. Our results provide experimental evidence for the classical theories of conformational transitions of polyelectrolytes and may find applications in many other polyelectrolyte-related researches.

Redox-Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the Presence of Glutathione.

The development of artificial nanomotor systems that are stimuli-responsive is still posing many challenges. Herein, we demonstrate the self-assembly of a redox-responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli-responsive nanomotors are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox-responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.

Drug-carrier interaction analysis in the cell penetrating peptide-modified liposomes for doxorubicin loading.

Doxorubicin (DOX) is widely used as an antitumor model drug in liposomes because of its high encapsulation efficiency. The cell-penetrating peptide (CPP) has potential applications in drug delivery systems. However, we discovered that the encapsulation efficiency of DOX decreased with increasing modification density of CPP on liposomes. To explore the interaction mechanisms of CPP-modified liposomes (CPPL) for DOX loading, X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were utilised, and theoretical calculations based on molecular dynamics simulation were performed. Results showed that the monomeric intermolecular interaction between CPP and DOX, in which the guanidinium group of CPP was parallel to the planar aromatic chromophore of DOX, depending on the cation-pi interaction and hydrogen bonds, weakened the tendency of DOX transporting into the internal medium from the liposomal external medium. Analysis of the interaction between CPP and DOX at the molecular level provided theoretical guidance for the further development of CPPL.

Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells.

Delivery vehicles that are able to actively seek and precisely locate targeted tissues using concentration gradients of signaling molecules have hardly been explored. The directed movement toward specific cell types of cargo-loaded polymeric nanomotors along a hydrogen peroxide concentration gradient (chemotaxis) is reported. Through self-assembly, bowl-shaped poly(ethylene glycol)-b-polystyrene nanomotors, or stomatocytes, were formed with platinum nanoparticles entrapped in the cavity while a model drug was encapsulated in the inner compartment. Directional movement of the stomatocytes in the presence of a fuel gradient (chemotaxis) was first demonstrated in both static and dynamic systems using glass channels and a microfluidic flow. The highly efficient response of these motors was subsequently shown by their directional and autonomous movement towards hydrogen peroxide secreting neutrophil cells.

Effect of local chain deformability on the temperature-induced morphological transitions of polystyrene-b-poly(N-isopropylacrylamide) micelles in aqueous solution.

The effect of temperature on the micellar morphology of two polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) diblock copolymers in an aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). At 25 °C, a mixture of vesicles and spheres are observed for the micelles of PS65-b-PNIPAM108, while PS65-b-PNIPAM360 exhibits mixed cylindrical and spherical micellar morphology. Upon increasing the temperature, the micellar morphology becomes spherical for PS65-b-PNIPAM108 at 60 °C and for PS65-b-PNIPAM360 at 40 °C. Such vesicle-to-sphere and cylinder-to-sphere transitions of micellar morphology are reversible when the micellar solutions are cooled back to 25 °C. However, these temperature-induced morphological transitions of the PS-b-PNIPAM micelles are contrary to the theoretical prediction. Qualitative analysis of the free energy shows that vesicular or cylindrical micelles tend to form at higher temperatures if only the overall volume change of the PNIPAM block is considered. The contradiction between the experimental results and theoretical prediction is interpreted in terms of the local deformability of the PNIPAM chains. At elevated temperatures, the collapsed PNIPAM globules are less deformable and must occupy larger areas at the micellar interface, although the overall volume is smaller at higher temperatures. This will lead to a larger repulsion between the PNIPAM globules and a remarkable increase in the free energy of the corona; thus, the formation of vesicles or cylinders at higher temperatures is prohibited.

A high-efficiency strategy for synthesizing cyclic polymers of methacryates in one pot.

An unprecedented strategy for the high-efficiency preparation of the cyclic polymers is developed. In this strategy, the atom transfer radical polymerization, the substitution of chain-end halide by azide group and Cu-catalyzed alkyne-azide cyclization, i.e., the frequently used three separated steps for the preparation of cyclic polymers, are integrated into a one-pot reaction by the introduction of a "regulator". The kernel of this novel strategy is the utilization of the different rates between the competitive ATRP propagation and SN 2 substitution of a tertiary-carbon halogen and secondary-carbon halogen. 0.55 g (yield = 59%) cyclic poly(methyl methacrylate) is obtained from 3.0 mL reaction solution. This work proposed a high-efficiency and bright promising strategy for the preparation of cyclic polymer, which would evoke more research interests on cyclic polymer.

Polymeric Micro/Nanomotors and Their Biomedical Applications.

Since their naissance in the 2000s, various micro or nanomotors with powerful functions have been proposed. Among them, polymer-based micro or nanomotors stand out for the easy processing and facile functionalization, holding immense potential for bioapplications. In this review, fabrication of polymer-based micro or nanomotors and their applications in biomedical areas are covered. Classic manufacturing approaches as well as cutting-edge techniques are discussed with representative works highlighted. Current challenges and future prospects are presented in the hope of pointing new research directions to facilitate practical translations of micro/nanomotors.

Biodegradability of Micro/Nanomotors: Challenges and Opportunities.

Micro/nanomotors (MNMs) are miniature machines that can convert chemical or external energy into their own mechanical motions. In previous decades, significant efforts have been made to improve the performance of MNMs. For practical applications, the biodegradability of MNMs is an important aspect that must be considered, particularly in the biomedical field. In this review, recent progress in the biodegradability of MNMs and their potential applications are summarized. Different biodegradable materials, including metals and polymers, or other strategies for the fabrication of MNMs, are presented. Current challenges and future perspectives are also discussed.

Nonequilibrium Reshaping of Polymersomes via Polymer Addition.

Polymersomes are a class of artificial liposomes, assembled from amphiphilic synthetic block copolymers, holding great promise toward applications in nanomedicine. The diversity in polymersome morphological shapes and, in particular, the precise control of these shapes, which is an important aspect in drug delivery studies, remains a great challenge. This is due to a lack of general methodologies that can be applied and the inability to capture the morphologies at the nanometer scale. Here, we present a methodology that can accurately control the shape of polymersomes via the addition of polyethylene glycol (PEG) under nonequilibrium conditions. Various shapes including spheres, ellipsoids, tubes, discs, stomatocytes, nests, stomatocyte-in-stomatocytes, disc-in-discs, and large compound vesicles (LCVs) can be uniformly captured by adjusting the water content and the PEG concentration. Moreover, these shapes undergo nonequilibrium changes in time, which is reflected in their phase diagram changes. This research provides a universal tool to fabricate all shapes of polymersomes by controlling three variables: water content, PEG concentration, and time. The use of the biofriendly polymer PEG enables the application of this methodology in the field of nanomedicine.

Thermoresponsive Brushes Facilitate Effective Reinforcement of Calcium Phosphate Cements.

Calcium phosphate ceramics are frequently applied to stimulate regeneration of bone in view of their excellent biological compatibility with bone tissue. Unfortunately, these bioceramics are also highly brittle. To improve their toughness, fibers can be incorporated as the reinforcing component for the calcium phosphate cements. Herein, we functionalize the surface of poly(vinyl alcohol) fibers with thermoresponsive poly(N-isopropylacrylamide) brushes of tunable thickness to improve simultaneously fiber dispersion and fiber-matrix affinity. These brushes shift from hydrophilic to hydrophobic behavior at temperatures above their lower critical solution temperature of 32 °C. This dual thermoresponsive shift favors fiber dispersion throughout the hydrophilic calcium phosphate cements (at 21 °C) and toughens these cements when reaching their hydrophobic state (at 37 °C). The reinforcement efficacy of these surface-modified fibers was almost double at 37 versus 21 °C, which confirms the strong potential of thermoresponsive fibers for reinforcement of calcium phosphate cements.

Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery.

We report the self-assembly of a biodegradable platinum nanoparticle-loaded stomatocyte nanomotor containing both PEG-b-PCL and PEG-b-PS as a potential candidate for anticancer drug delivery. Well-defined stomatocyte structures could be formed even after incorporation of 50% PEG-b-PCL polymer. Demixing of the two polymers was expected at high percentage of semicrystalline poly(ε-caprolactone) (PCL), resulting in PCL domain formation onto the membrane due to different properties of two polymers. The biodegradable motor system was further shown to move directionally with speeds up to 39 µm/s by converting chemical fuel, hydrogen peroxide, into mechanical motion as well as rapidly delivering the drug to the targeted cancer cell. Uptake by cancer cells and fast doxorubicin drug release was demonstrated during the degradation of the motor system. Such biodegradable nanomotors provide a convenient and efficient platform for the delivery and controlled release of therapeutic drugs.

Poly(beta-alanoid-block-beta-alanine)s: synthesis via cobalt-catalyzed carbonylative polymerization and self-assembly.

The titled diblock copolymers are synthesized via cobalt-catalyzed living carbonylative polymerization of N-alkylaziridines under moderate pressures followed by a deprotection step. The poly(beta-alanine) block is solubilized by the poly(beta-alanoid) block in chloroform and remains fully hydrogen-bonded in the form of a sheet-like assembly.