Intraocular Lens with Mussel-Inspired Coating for Preventing Posterior Capsule Opacification via Photothermal Effect.

Phacoemulsification with implantation of intraocular lens (IOLs) has been widely applied as a standard treatment for cataract, which is the leading cause of vision impairment. However, it still remains a critical challenge to prevent posterior capsule opacification (PCO) in terms of postoperative visual quality. Herein, we report IOLs with mussel-inspired coatings for inhibiting lens epithelial cells and then preventing PCO through photothermal conversion effect. The mussel-inspired coatings are deposited on the nonoptical surface areas of IOLs, endowing the modified IOLs with efficient photothermal conversion property. The temperature can be facilely raised to 50-60 °C for the photothermal IOLs (PT-IOLs) by near-infrared (NIR) laser irradiation at a safe intensity of 0.3 W/cm2. These PT-IOLs display high capability of inhibiting lens epithelial cells (LECs) in vitro. Therefore, under routine NIR laser irradiation, New Zealand white rabbits implanted with the PT-IOLs demonstrate significantly lower evaluation of PCO (EPCO) scores than the control groups. The overall results indicate that our PT-IOLs provide a promising choice for the clinical prevention of PCO, thus opening a way to maintain the postoperative visual qualities for cataract patients.

Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells.

Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis, angiosteosis, and vascular aging. Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell. Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering, regenerative medicine, and medical devices. Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells (VECs) and smooth muscle cells (VSMCs). Interestingly, our findings demonstrate that, with the increase of substrate stiffness, the autophagy level of VECs and VSMCs showed differential changes: endothelial autophagy levels reduced, leading to the reductions in a range of gene expression associated with endothelial function; while, autophagy levels of VSMCs increased, showing a transition from contractile to the synthetic phenotype. We further demonstrate that, by inhibiting cell autophagy, the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased, suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing. Although the underlying mechanism requires further study, this work highlights the relationship of substrate stiffness, autophagy, and vascular cell behaviors, and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications.

Dynamic Porous Pattern through Controlling Noncovalent Interactions in Polyelectrolyte Film for Sequential and Regional Encapsulation.

Inspired by nature, many functional surfaces have been developed with special structures in biology, chemistry, and materials. Many research studies have been focused on the preparation of surfaces with static structure. Achieving dynamical manipulation of surface structure is desired but still a great challenge. Herein, a polyelectrolyte film capable of regional and reversible changes in the microporous structure is presented. Our proposal is based on the combination of azobenzene (Azo) π-π stacking and electrostatic interaction, which could be affected respectively by ultraviolet (UV) irradiation and water plasticization, to tune the mobility of polyelectrolyte chains. The porous patterns can be obtained after regional ultraviolet irradiation and acid treatment. Owing to the reversibility of Azo π-π stacking and electrostatic interaction, the patterns can be repeatedly created and erased in the polyelectrolyte film made by layer-by-layer (LbL) self-assembly of poly(ethyleneimine)-azo and poly(acrylic acid). Furthermore, through two rounds of porous pattern formation and erasure, different functional species can be loaded separately and confined regionally within the film, showing potential applications in the functional surface. This work highlights the coordination of two noncovalent interactions in thin films for regional and reversible controlling its structure, opening a window for more in-depth development of functional surfaces.

Relief of Biofilm Hypoxia Using an Oxygen Nanocarrier: A New Paradigm for Enhanced Antibiotic Therapy.

Biofilms are chief culprits of most intractable infections and pose great threats to human health. Conventional antibiotic therapies are hypodynamic to biofilms due to their strong drug resistance, closely related with biofilm hypoxia. A new strategy for enhanced antibiotic therapy by relieving biofilm hypoxia is reported here. A two-step sequential delivery strategy is fabricated using perfluorohexane (PFH)-loaded liposomes (lip) as oxygen (O2) carriers (denoted as lip@PFH@O2) and commercial antibiotics. The results indicate that the two-step sequential treatment exhibits much lower minimum bactericidal concentrations than the antibiotic treatment alone. In this design, the lip@PFH@O2 holds positively charged surface for better biofilm penetration. After penetrating into biofilm, oxygen can be released from lip@PFH@O2 by inches, which greatly relieves biofilm hypoxia. With the relief of hypoxia, the quorum sensing and the drug efflux pumps of bacteria are suppressed by restraining related gene expression, leading to the reduced antibiotic resistance. Furthermore, the in vivo experimental results also demonstrate that lip@PFH@O2 can effectively relieve biofilm hypoxia and enhance therapeutic efficacy of antibiotics. As a proof-of-concept, this research provides an innovative strategy for enhanced antibiotic therapy by relieving hypoxia, which may hold a bright future in combating biofilm-associated infections.

Fabrication and wetting behaviour of micro/nanostructured mushroom-shaped silver pillar surface.

This manuscript presents a simple, one-step method for the fabrication of micro/nanostructured metal-based superhydrophobic surfaces via electroplating using stacked polycarbonate membranes with nanoscale and microscale pores as a template. The two-tiered mushroom-shaped silver pillar arrays include a top layer composed of nanopillars and a bottom layer composed of T-shaped micropillars. The presence of the re-entrant surface structures with a strong resistance pin the droplets to the cap's ridge and prevent water droplets from penetrating into the valleys of the rough surface, thus resulting in an increase in water contact angle (WCA). Compared with microstructured mushroom-shaped surfaces (WCA = 148°, sliding angle (SA) âˆ¼ 26°) and nanostructured surfaces (WCA = 151.5°, SA âˆ¼ 4.8°), the micro/nanostructured mushroom-shaped pillar arrays (WCA = 154.1°, SA âˆ¼ 2°) exhibit remarkable superhydrophobic properties with high CA and low SA. This new micro/nanostructured surface will have a potential application in metal-based superhydrophobic materials.

Polymyxin B-Polysaccharide Polyion Nanocomplex with Improved Biocompatibility and Unaffected Antibacterial Activity for Acute Lung Infection Management.

The decade-old antibiotic, polymyxin B (PMB), is regarded as the last line defense against gram-negative "superbug." However, the serious nephrotoxicity and neurotoxicity strongly obstruct further application of this highly effective antibiotic. Herein, a charge switchable polyion nanocomplex exhibiting pH-sensitive property is proposed to deliver PMB which is expected to improve the biosafety of PMB on the premise of retaining excellent antibacterial activity. The polyion nanocomplex is prepared through electrostatic interaction of positively charged PMB and negatively charged 2,3-dimethyl maleic anhydride (DA) grafted chitoligosaccharide (CS). The negative charge of CS-DA will convert to positive due to the hydrolysis of amide bonds in acidic infectious environment, leading to the disassembly of CS-DA/PMB nanocomplex and release of PMB. CS-DA/PMB nanocomplex does not show significant toxicity to mammalian cells while retaining excellent bactericidal capability equivalent to free PMB. The nephrotoxicity and neurotoxicity of CS-DA/PMB dramatically decrease compared to free PMB. Moreover, CS-DA/PMB nanocomplex exhibits superior bactericidal activity against Pseudomonas aeruginosa in an acute lung infection mouse model. The pH-sensitive polyion nanocomplexes may provide a new way to reduce the side effects of highly toxic antibiotics without reducing their intrinsic antibacterial activity, which is the key factor to achieve extensive in vivo clinical applications.

Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms.

Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilms. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into an acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive α-cyclodextrin (α-CD) conjugated nitric oxide (NO) prodrug (α-CD-NO) and chlorin e6 (Ce6) prodrug (α-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)2-DA) via host-guest interaction, the supramolecular nanocarrier α-CD-Ce6-NO-DA was finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into the biofilm. Once infiltrated into the biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in the biofilm, which not only produces abundant NO for killing bacteria but also reduces the biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), further improving the PDT efficiency. Due to the effective penetration into the biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at a low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.

Bacteria-Targeted Supramolecular Photosensitizer Delivery Vehicles for Photodynamic Ablation Against Biofilms.

Photodynamic therapy (PDT) is believed to be a potent method for biofilm treatments. However, undesired damage to normal cells may be caused due to the nonselective nature of PDT. Therefore, targeted PDT is preferred on one hand to enhance antimicrobial effects and on the other hand to reduce cytotoxicity to normal cells. For this purpose, novel bacteria-targeted photosensitizer delivery micelles are fabricated, taking advantage of α-cyclodextrin (α-CD)/polyethylene glycol (PEG) supramolecular assembly. Hydrophilic antimicrobial peptide (AMP) Magainin I is covalently bound with PEG, working as a bacterial targeting group as well as the stabilizing shell of the supramolecular micelles. Photosensitizer Chlorin e6 (Ce6) is grafted onto α-CD. The micelles exhibit excellent bacterial targeting effects. Compared to α-CD-Ce6, the supramolecular micelles possess enhanced biofilm killing ability against Gram (-) Pseudomonas aeruginosa biofilms and Gram (+) methicillin-resistant Staphylococcus aureus (MRSA) biofilms while reducing cytotoxicity to NIH/3T3 model cells.

Photothermal Killing of Methicillin-Resistant Staphylococcus aureus by Bacteria-Targeted Polydopamine Nanoparticles with Nano-Localized Hyperpyrexia.

Bacterial infections caused by antibiotic-resistant pathogens have become intractable problems to public health. Therefore, there is an imperious demand for developing new approaches to effectively kill antibiotic-resistant bacteria. In this work, we report a kind of bacteria-targeted polydopamine nanoparticle exhibiting great photothermal killing ability toward methicillin-resistant Staphylococcus aureus (MRSA) by nano-localized hyperpyrexia under low-power near-infrared (NIR) light irradiation. These bacteria-targeted nanoparticles (PDA-PEG-Van) are prepared by modifying polydopamine nanoparticles with thiol-poly(ethylene glycol) (mPEG-SH) and vancomycin (Van) molecules. The PEG shell endows the nanoparticles with excellent long-term circulation stability. Due to the multivalent hydrogen-bond interactions between vancomycin and the MRSA cell wall, the vancomycin-modified polydopamine nanoparticles can specifically target MRSA rather than mammalian cells. These bacteria-targeted nanoparticles are employed as a nano-localized heat source to kill MRSA via disrupting the bacterial cell wall and membrane under irradiation of low-power NIR light. More importantly, the surrounding healthy tissues suffer bare damage, owing to the absence of any targeting effect of PDA-PEG-Van toward mammalian cells and the low power of NIR light used in the therapeutic process. Given the above advantages, the bacteria-targeted polydopamine nanoparticles proposed in this work show tremendous potential to treat MRSA infections, because they can effectively limit localized heating in the infection sites to kill bacteria and cut down damage to healthy tissues.

Polyphenol-Assisted Exfoliation of Transition Metal Dichalcogenides into Nanosheets as Photothermal Nanocarriers for Enhanced Antibiofilm Activity.

Transition metal dichalcogenide (TMD) nanosheets have evoked enormous research enthusiasm and have shown increased potentials in the biomedical field. However, a great challenge lies in high-throughput, large-scale, and eco-friendly preparation of TMD nanosheet dispersions with high quality. Herein, we report a universal polyphenol-assisted strategy to facilely exfoliate various TMDs into monolayer or few-layer nanosheets. By optimizing the exfoliation condition of molybdenum disulfide (MoS2), the yield and concentration of as-exfoliated nanosheets are up to 60.5% and 1.21 mg/mL, respectively. This is the most efficient aqueous exfoliation method at present and is versatile for the choices of polyphenols and TMD nanomaterials. The as-exfoliated MoS2 nanosheets possess superior biomedical stability as nanocarriers to load antibiotic drugs. They show a high photothermal conversion effect and thus induce a synergetic effect of chemotherapy and photothermal therapy to harvest enhanced antibiofilm activity under near-infrared (NIR) light. All these results offer an appealing strategy toward the synthesis and application of ultrathin TMD nanosheets, with great implications for their development.

Dopamine-Triggered One-Step Polymerization and Codeposition of Acrylate Monomers for Functional Coatings.

Surface modification has been well recognized as a promising strategy to design and exploit diversified functional materials. However, conventional modification strategies usually suffer from complicated manufacture procedures and lack of universality. Herein, a facile, robust, and versatile approach is proposed to achieve the surface functionalization using dopamine and acrylate monomers via a one-step polymerization and codeposition process. The gel permeation chromatography, proton nuclear magnetic resonance, liquid chromatography-mass spectrometry, and UV-visible spectra results indicate that dopamine possesses the capability of triggering the polymerization of acrylate monomers into high-molecular-weight products, and the inherent adhesive ability of polydopamine can assist the polymerized products to deposit on various substrates. Besides, protein-resistant, antibacterial, and cell adhesion-resistant surfaces can be easily fabricated via the finely designed integration of corresponding acrylate monomers into the codeposition systems. This approach of in situ polymerization and codeposition significantly simplifies the fabrication process and provides more manifold choices for surface modification, which will open a new door for broadening the applications of polydopamine-based coatings.

Surface-Adaptive Gold Nanoparticles with Effective Adherence and Enhanced Photothermal Ablation of Methicillin-Resistant Staphylococcus aureus Biofilm.

Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.