Multifunctional Polymer Vesicles for Synergistic Antibiotic-Antioxidant Treatment of Bacterial Keratitis.

As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic-antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant-antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections.

Seeded RAFT Polymerization-Induced Self-assembly: Recent Advances and Future Opportunities.

Over the past decade, polymerization-induced self-assembly (PISA) has fully proved its versatility for scale-up production of block copolymer nanoparticles with tunable sizes and morphologies; yet, there are still some limitations. Recently, seeded PISA approaches combing PISA with heterogeneous seeded polymerizations have been greatly explored and are expected to overcome the limitations of traditional PISA. In this review, recent advances in seeded PISA that have expanded new horizons for PISA are highlighted including i) general considerations for seeded PISA (e.g., kinetics, the preparation of seeds, the selection of monomers), ii) morphological evolution induced by seeded PISA (e.g., from corona-shell-core nanoparticles to vesicles, vesicles-to-toroid, disassembly of vesicles into nanospheres), and iii) various well-defined nanoparticles with hierarchical and sophisticated morphologies (e.g., multicompartment micelles, porous vesicles, framboidal vesicles, AXn -type colloidal molecules). Finally, new insights into seeded PISA and future perspectives are proposed.

Foldable Bulk Anti-adhesive Polyacrylic Intraocular Lens Material Design and Fabrication for Posterior Capsule Opacification Prevention.

Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention. Herein, a new anti-adhesive IOL material was designed and successfully synthesized by radical copolymerization of ethylene glycol phenyl ether methacrylate (EGPEMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA). The physicochemical properties of P(EGPEMA-co-EA) copolymer materials, including chemical structure, mechanical, thermal, surface, and optical properties, were analyzed by using 1H NMR spectroscopy, FT-IR spectroscopy, tensile test, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), water contact angle measurement, and UV-vis spectroscopy. The elongation at break and the modulus of elasticity of the copolymer were tunable through the change of the composition of monomers. Compared to other components, the tensile results showed that P(EGPEMA-co-EA) materials (70% EGPEMA in mass ratio, F7) are suitable for the preparation of foldable intraocular lens with lower elastic modulus and higher elongation at break. TGA and DSC showed that the material has high thermal stability, and the glass transition temperature of F7 material is 16.1 °C. The water contact angle measurement results showed that the introduction of EA improved the hydrophilicity of the material. The percentage of transmittance of all copolymers at 400-800 nm is above 85%. Then, the biocompatibility of the materials was evaluated by in vitro assay and subcutaneous implantation. Both in vitro results and subcutaneous implantation experiments showed that the designed IOL materials exhibited a good anti-adhesion effect and no cytotoxicity. Finally, phacoemulsification and IOL intraocular implantation were performed, and the in vivo results confirmed the good PCO prevention ability as well as the biocompatibility of the new IOL materials.

Constructing Cylindrical Nanostructures Via Directional Morphology Evolution Induced by Seeded Polymerization.

Herein, spindle-shaped block copolymer (BCP) nanoparticles are used in seeded polymerization of methyl methacrylate as a novel approach to generating cylindrical nanostructures. The chain-extension of BCP seeds by an amorphous coil-type polymer within the seed core composed of semifluorinated liquid-crystalline blocks triggers the deforming, stretching, and directional growth of the seeds along the long axis, eventually leads to nanorods.

Maintenance of amyloid ß peptide homeostasis by artificial chaperones based on mixed-shell polymeric micelles.

The disruption of Aß homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer's disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis in vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed-shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM-based chaperones can maintain Aß homeostasis by a combination of inhibiting Aß fibrillation and facilitating Aß aggregate clearance and simultaneously reducing Aß-mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect.

Surface Self-Assembly Construction of Therapeutic Contact Lens with Bacterial "Kill-Releasing" and Drug-Reloading Capabilities for Efficient Bacterial Keratitis Treatment.

Bacterial keratitis, an ophthalmic emergency, can cause corneal perforation and even endophthalmitis, thus leading to severe visual impairment. To achieve effective treatment of bacterial keratitis, good bioavailability of antimicrobial drugs on the ocular surface is desired. In this investigation, a layer-by-layer (LBL) self-assembly combined with the host-guest recognition was used to construct an antibacterial coating on the surface of corneal contact lens (CLs) to improve drug bioavailability and achieve successful treatment of bacterial keratitis. First, a radical copolymerization of acrylic acid (AA) and 1-adamantan-1-ylmethyl acrylate (AdA) was carried out to synthesize a polyanionic copolymer P(AA-co-AdA) (defined as PAcA). Then, PAcA copolymer combined with poly(ethyleneimine) (PEI) was used for a layer-by-layer (LBL) self-assembly to fabricate multilayer films on the surface of CLs. An antibacterial conjugate, ß-cyclodextrin-levofloxacin (ß-CD-LEV), was successfully synthesized and utilized to generate antibacterial coating through a host-guest interaction between AdA and ß-CD-LEV. The antibacterial ability and treatment effect of bacterial keratitis was evaluated by in vitro assay and in vivo test in an animal model of staphylococcal keratitis, demonstrating that the antibacterial coating had good antibacterial and germicidal efficacy both in vivo and in vitro. We believe that this work will provide a promising strategy for the treatment of bacterial keratitis.

A polydopamine-based photodynamic coating on the intraocular lens surface for safer posterior capsule opacification conquering.

Intraocular lens (IOL) is the indispensable implant for cataract surgery. However, posterior capsular opacification (PCO) happens in high incidence after IOL implantation. PCO is caused by adhesion, proliferation, and trans-differentiation of the residual human lens epithelial cells (HLECs). Despite the great achievements in surface coating and antiproliferative drug loading on the intraocular lens (IOL) for effective PCO prevention, the complex fabrication process and potential toxicity of the drugs still limit their clinical applications and commercial mass production. In this investigation, a convenient and efficient photodynamic therapy (PDT) coating fabricated by facile yet economical and practical dopamine self-polymerization was applied to IOL surface modification for PCO prevention. The optical properties of IOL, such as light transmittance, imaging quality and refractive index, remain unchanged after modification. Using an in vitro cell assay, the parameters of PDT were optimized. The PDT coating shows excellent biocompatibility in darkness and eliminates LECs significantly under irradiation. The research on the cell elimination mechanism showed that reactive oxygen species (ROS) mainly induced cell apoptosis. In vivo experiments demonstrated that the implantation of modified IOLs can prevent PCO effectively. As a result, this work provides a safe, simple and effective PDT coating for the IOL surface to reduce the incidence of PCO.

Biocompatible Hydrogels Based on Food Gums with Tunable Physicochemical Properties as Scaffolds for Cell Culture.

Hydrogels composed of food gums have gained attention for future biomedical applications, such as targeted delivery and tissue engineering. For their translation to clinical utilization, reliable biocompatibility, sufficient mechanical performance, and tunable structure of polysaccharide hydrogels are required aspects. In this work, we report a unique hybrid polysaccharide hydrogel composed of salecan and curdlan, in which the former is a thickening agent and the latter serves as a network matrix. The physicochemical properties, such as mechanical strength, thermal stability, swelling, and morphology, of the developed composite hydrogel can be accurately modulated by varying the polysaccharide content. Importantly, cytotoxicity assays show the non-toxicity of this hybrid hydrogel. Furthermore, this hydrogel system can support cell proliferation, migration, and function. Altogether, our work proposes a new strategy to build a polysaccharide-constructed hydrogel scaffold, which holds much promise for tissue engineering in terms of cell engraftment, survival, proliferation, and function.

Facile formation of salecan/agarose hydrogels with tunable structural properties for cell culture.

Salecan polysaccharide produced by Agrobacterium sp. ZX09 is an attractive biopolymer to construct hydrogel scaffolds for cell culture. However, some limitations such as poor mechanical performance, complicated fabrication process and slow gelation times still exist in the biomedical applications of microbial-based salecan polysaccharide hydrogels. Here, a series of polysaccharide hydrogels composed of salecan and agarose with adjustable structural properties are designed. The resultant hybrid salecan/agarose hydrogels exhibit controllable physical and chemical properties including thermal stability, water uptake, mechanical strength and microarchitecture, which can be readily realized with minimum change of the polysaccharide content. Furthermore, cytotoxicity assays reveal that the designed composite hydrogels are non-toxic. More importantly, these hydrogels support cell survival, proliferation, and migration. Together, this work opens up a new avenue to build polysaccharide hydrogel platforms for tissue engineering.

A biocompatible cobaltporphyrin-based complex micelle constructed via supramolecular assembly for oxygen transfer.

Herein, a complex micelle as an oxygen nano-carrier is constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys), tetrakis(4-sulfonatophenyl)porphinato cobalt(ii) (Co(ii)TPPS), a heptapeptide (Cys-His-His-His-His-His-His) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD). Co(ii)TPPS was encapsulated into the cavities of TM-ß-CDs driven by the host-guest interaction so that the irreversible formation of a µ-oxo-dimer of Co(ii)TPPS can be effectively prevented. The imidazole groups of the heptapeptide were selected as good axial ligands coordinating to the centric cobalt of Co(ii)TPPS, which subtly constituted the five-coordinated precursor serving as an active functional centre for oxygen binding. The sixth position of Co(ii)TPPS can bind oxygen. Furthermore, the host-guest inclusion (TM-ß-CD/Co(ii)TPPS) was loaded into the hydrophobic core of the complex micelle and tightly fixed with PLys chains. The hydrophilic PEG blocks stretched in the aqueous solution constitute the shells which stabilize the structure of the complex micelle as well as impart the complex micelle sufficient blood circulation time. Moreover, the complex micelle exhibited excellent biocompatibility and cellular uptake. Therefore, the rationally designed amphiphilic structure can work as promising artificial O2 carriers in vivo. Potentially, the complex micelle can be expected to change the anaerobic microenvironment and find applications in the repair of the cells damaged by cellular hypoxia.

Effect of the Surface Charge of Artificial Chaperones on the Refolding of Thermally Denatured Lysozymes.

Artificial chaperones are of great interest in fighting protein misfolding and aggregation for the protection of protein bioactivity. A comprehensive understanding of the interaction between artificial chaperones and proteins is critical for the effective utilization of these materials in biomedicine. In this work, we fabricated three kinds of artificial chaperones with different surface charges based on mixed-shell polymeric micelles (MSPMs), and investigated their protective effect for lysozymes under thermal stress. It was found that MSPMs with different surface charges showed distinct chaperone-like behavior, and the neutral MSPM with PEG shell and PMEO2MA hydrophobic domain at high temperature is superior to the negatively and positively charged one, because of the excessive electrostatic interactions between the protein and charged MSPMs. The results may benefit to optimize this kind of artificial chaperone with enhanced properties and expand their application in the future.

Hemin-block copolymer micelle as an artificial peroxidase and its applications in chromogenic detection and biocatalysis.

Following an inspiration from the fine structure of natural peroxidases, such as horseradish peroxidase (HRP), an artificial peroxidase was constructed through the self-assembly of diblock copolymers and hemin, which formed a functional micelle with peroxidase-like activity. The pyridine moiety in block copolymer poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP) can coordinate with hemin, and thus hemin is present in a five-coordinate complex with an open site for binding substrates, which mimics the microenvironment of heme in natural peroxidases. The amphiphilic core-shell structure of the micelle and the coordination interaction of the polymer to the hemin inhibit the formation of hemin µ-oxo dimers, and thereby enhance the stability of hemin in the water phase. Hemin-micelles exhibited excellent catalytic performance in the oxidation of phenolic and azo compounds by H2O2. In comparison with natural peroxidases, hemin-micelles have higher catalytic activity and better stability over wide temperature and pH ranges. Hemin-micelles can be used as a detection system for H2O2 with chromogenic substrates, and they anticipate the possibility of constructing new biocatalysts tailored to specific functions.