Self-Assembled Borneol-Guanidine-Based Amphiphilic Polymers as an Efficient Antibiofilm Agent.

Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGNx-n) possess strong antibacterial activity and can eliminate mature Staphylococcus aureus (S. aureus) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGNx-n. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGNx-n polymers, which enhances their ability to penetrate biofilms. BGNx-n nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 µg·mL-1 against S. aureus and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.

Long-Lasting Antibacterial PDMS Surfaces Constructed from Photocuring of End-Functionalized Polymers.

A challenge remains in the development of anti-infectious coatings for the inert surfaces of biomedical devices that are prone to bacterial colonization and biofilm formation. Here, a facile photocuring method to construct functionalized polymeric coatings on inert polydimethylsiloxane (PDMS) surfaces, is developed. Using atom transfer radical polymerization (ATRP) initiator bearing thymol group, hydrophilic DMAEMA and benzophenone (BP)-containing monomers are copolymerized to form polymers with end functional groups. An end-functionalized biocidal coating is then constructed on the inert PDMS surface in one step using a photocuring reaction. The functionalized PDMS surfaces show excellent antibacterial and antifouling properties, are capable of completely eradiating MRSA within ≈6 h, and effectively inhibit the growth of biofilms. In addition, they have good stability and long-lasting antibacterial activity in body fluid environments such as 0.9% saline and urine. According to bladder model experiments, the catheter's lifespan can be extended from ≈7 to 35 days by inhibiting the growth and migration of bacteria along its inner surface. The photocuring technique is therefore very promising in terms of surface functionalization of inert biomedical devices in order to minimize the spread of infection.

Bacteria-targeted photothermal therapy for combating drug-resistant bacterial infections.

Photothermal therapy is an ideal non-invasive treatment for bacterial infections. However, if photothermal agents are unable to target bacteria, they can also cause thermal damage to healthy tissue. This study describes the fabrication of a Ti3C2Tx MXene-based photothermal nanobactericide (denoted as MPP) that targets bacteria by modifying MXene nanosheets with polydopamine and the bacterial recognition peptide CAEKA. The polydopamine layer blunts the sharp edges of MXene nanosheets, preventing their damage to normal tissue cells. Furthermore, as a constituent of peptidoglycan, CAEKA can recognize and penetrate the bacterial cell membrane based on similar compatibility. The obtained MPP exhibits superior antibacterial activity and high cytocompatibility compared to the pristine MXene nanosheets. In vivo studies showed that MPP colloidal solution under 808 nm NIR light can effectively treat a subcutaneous abscess caused by multi-drug resistant bacterial infection without adverse effects.

Citronellol-Based Long-Lasting Antibacterial Cotton Fabrics without Bacterial Resistance.

Antibacterial cotton helps prevent the growth and spread of harmful microorganisms, reduces the risk of infection, and has a prolonged service life by reducing bacterial degradation. However, most antibacterial agents used are toxic to humans and the environment. Citronellol-poly(N,N-dimethyl ethyl methacrylate) (CD), a highly effective antibacterial polymer, is synthesized from natural herbal essential oils (EOs). CD exhibited efficient, rapid bactericidal activity against Gram-positive, Gram-negative, and drug-resistant bacteria. Citronellol's environmental benignity makes CDs less hemolytic. Notably, negligible drug resistance developed after 15 bacterial subcultures. The CD-treated cotton fabric displayed better antibacterial performance than AAA-grade antibacterial fabric, even after repeated washing. This study extends the practical application of EOs to antibacterial surfaces and fabrics, which is promising for use in personal care products and medical settings.

Multiple Pickering emulsions stabilized by surface-segregated micelles with adaptive wettability.

Surface-segregated micelles (SSMs) with adaptive wettability have considerable potential for application in Pickering emulsions and bioanalytical technology. In this study, spherical SSMs were prepared via polymerization-induced self-assembly co-mediated with a binary mixture of macromolecular chain transfer agents: pH-responsive poly(2-(dimethylamino) ethyl methacrylate) and hydrophobic polydimethylsiloxane. Using these SSMs as the sole emulsifier, we adjusted the pH to successfully produce both water-in-oil-in-water (W/O/W) and oil-in-water-in-oil (O/W/O) multiple emulsions through a single-step emulsification process. Moreover, we demonstrated that multiple emulsion systems with adjustable pH are suitable for the development of an efficient and recyclable interfacial catalytic system. Multiple emulsion microreactors increase the area of the oil-water interface and are therefore more efficient than the commonly used O/W and W/O emulsion systems.

Low-Temperature Photothermal Therapy Based on Borneol-Containing Polymer-Modified MXene Nanosheets.

Noninvasive photothermal therapy (PTT) is an emerging strategy for eliminating multidrug-resistant (MDR) bacteria that achieve sterilization by generating temperatures above 50 °C; however, such a high temperature also causes collateral damage to healthy tissues. In this study, we developed a low-temperature PTT based on borneol-containing polymer-modified MXene nanosheets (BPM) with bacteria-targeting capabilities. BPM was fabricated through the electrostatic coassembly of negatively charged two-dimensional MXene nanosheets (2DM) and positively charged quaternized α-(+)-borneol-poly(N,N-dimethyl ethyl methacrylate) (BPQ) polymers. Integrating BPQ with 2DM improved the stability of 2DM in physiological environments and enabled the bacterial membrane to be targeted due to the presence of a borneol group and the partially positive charge of BPQ. With the aid of near-infrared irradiation, BPM was able to effectively eliminate methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) through targeted photothermal hyperthermia. More importantly, BPM effectively eradicated more than 99.999% (>5 orders of magnitude) of MRSA by localized heating at a temperature that is safe for the human body (≤40 °C). Together, these findings suggest that BPM has good biocompatibility and that membrane-targeting low-temperature PTT could have great therapeutic potential against MDR infections.

Nanocomposite Polymer Colloids Prepared via Emulsion Polymerization and Stabilized Using Polydopamine-Coated Silica Particles.

Polymer/inorganic colloidal nanocomposites can be prepared via Pickering emulsion polymerization (PEP); however, this process usually requires the use of surfactants, auxiliary comonomers, and volatile organic compounds. Herein, we report a versatile and efficient method for synthesizing stable monodisperse polymer/silica colloidal nanocomposite particles via PEP. First, silica nanoparticles were modified by depositing a multifunctional polydopamine (PDA) film. The outermost PDA film could enhance the precipitation of oligomeric polymer radicals on the silica surface, which is crucial for the preparation of stable polymer/inorganic colloidal nanocomposites via PEP. Notably, this PDA modification approach can employ different initiator systems, such as cationic initiators and redox initiator couples, and can be applied to various monomers and monomer pairs (St, St/nBA, MMA, MMA/nBA, Vac, Vac/nBA). The influence of the concentration and size of polydopamine-coated silica (SiO2@PDA) on the colloidal nanocomposite was investigated. Increasing the diameter of SiO2@PDA and decreasing the concentration of SiO2@PDA both lead to the formation of larger nanocomposite particles. Considering its wide applicability, the proposed PDA modification approach can be applied to other functional inorganic particles to prepare multifunctional polymer/inorganic nanocomposite particles.

Durable Antibacterial Cotton Fabrics Based on Natural Borneol-Derived Anti-MRSA Agents.

Borneol, a natural extract with unique bicyclic monoterpene structure, has attracted increasing attention due to its broad-spectrum antibacterial properties via membrane disruption mechanism. However, the negligible water solubility of borneol limits its antibacterial efficiency. Herein, borneol-based water-soluble antibacterial agents are designed and synthesized to combat multi-drug resistant bacteria. The integration of borneol with hydrophilic poly(N,N-dimethylethyl methacrylate) (PDMAEMA) polymer chains boosts the antibacterial capability of borneol against Gram-negative, Gram-positive, and even multi-drug resistant bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) are completely killed upon treatment with 50 µg mL-1 of borneol-based polymers and Escherichia coli are annihilated at 39 µg mL-1 . It is further demonstrated that the borneol-based antibacterial agents can be grafted onto cotton fabrics as a nonleaching antibacterial agent, which have higher sustained antibacterial activity than cotton fabrics coated with the commercial quaternary ammonium finishing agents (AEM 5700). The functionalized fabrics with excellent bactericidal activity, especially against MRSA, may have great potential applications in managing hospital-acquired infections.

On-Demand Oil-Water Separation by Environmentally Responsive Cotton Fabrics.

Environmentally responsive cotton fabrics were fabricated by dip-coating ABC miktoarm star terpolymers, which contain reactive poly(3-triisopropyloxysilylpropyl methacrylate) blocks, hydrophobic poly(dimethylsiloxane) (PDMS) blocks, and hydrophilic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) blocks. The functionalized cotton fabrics with perfectly alternating PDMS and PDMAEMA blocks show underoil superhydrophobicity and underwater superoleophobicity. The wettability and permeability of the functionalized fabrics can be readily adjusted by the contacting medium. More interestingly, surface reconstruction causes a reduction in the breakthrough pressure of the nonwetting phase. The adaptive permeability endows the functionalized cotton fabrics with the capability to separate heavy oil-water-light oil ternary mixtures.

All-Silica Submicrometer Colloidosomes for Cargo Protection and Tunable Release.

Colloidosomes have received considerable attention for the controlled delivery of active ingredients in medicine, agrochemicals, and cosmetics. However, most reported colloidosomes are highly permeable and size is larger than 1 µm. All silica colloidosomes have now been prepared with adjustable size, compact shell and low permeability. Our approach is based on the formation of inverse water-in-oil (w/o) emulsions stabilized solely by hydrophobic silica nanoparticles and subsequent locking of the particle at the oil-water interface by a simple sol-gel reaction of silica precursor at room temperature. The colloidosomes obtained display a robust and closed shell, ensuring a long-term retention of small hydrophilic molecules such as Methylene Blue. Remarkably, unlike all other reported silica colloidosomes, a timely and stepwise release of the encapsulated cargo can be triggered by adding ethanol or surfactant without destroying the capsule shell.

Submicron Inverse Pickering Emulsions for Highly Efficient and Recyclable Enzymatic Catalysis.

Herein, we report the utilization of a submicron Pickering emulsion (SPE) for the encapsulation of enzymes (e.g., lipase from Candida sp.) in water droplets that were solely stabilized by hydrophobic solid or mesoporous silica nanoparticles in toluene for use in biphasic reactions. The catalytic performance of encapsulated lipase was evaluated in the esterification of 1-hexanol and hexanoic acid under stirring-free conditions, which was favorable for maintaining enzymatic activity. Remarkably, the SPE significantly increased the specific activity of encapsulated lipase, owing to the exceptionally high water/oil interfacial area and short diffusion distance of the reagents in the SPE. With mesoporous silica nanoparticles, the activity of lipase was approximately 25.5- and 2.8-times higher than that of free lipase and encapsulated lipase in the micron Pickering emulsion, respectively. The higher water/toluene interfacial area was attributed to the smaller submicron-scale water droplets and the increase in the mass transfer of enzymes or substrates was further improved by using mesoporous Pickering stabilizers. In addition, the encapsulated lipase in SPE also demonstrated excellent stability and could be recycled up to 15 times without significant loss of activity.

Tailoring the Wettability of Colloidal Particles for Pickering Emulsions via Surface Modification and Roughness.

Pickering emulsions are water or oil droplets that are stabilized by colloidal particles and have been intensely studied since the late 90s. The surfactant-free nature of these emulsions has little adverse effects such as irritancy and contamination of environment and typically exhibit enhanced stability compared to surfactant-stabilized emulsions. Therefore, they offer promising applications in cosmetics, food science, controlled release, and the manufacturing of microcapsules and porous materials. The wettability of the colloidal particles is the main parameter determining the formation and stability of Pickering emulsions. Tailoring the wettability by surface chemistry or surface roughness offers considerable scope for the design of a variety of hybrid nanoparticles that may serve as novel efficient Pickering emulsion stabilizers. In this review, we will discuss the recent advances in the development of surface modification of nanoparticles.

Shear-Assisted Fabrication of Block Copolymer Agglomerates with Various Morphologies in Viscous Medium.

In this work, we have investigated the effect of laminar flow shearing on the formation of block copolymer agglomerates in viscous medium. Under a laminar flow shearing, the block copolymer solution droplets were spontaneously emulsified and were then elongated into protofibers, which in turn transformed into particles with various morphologies. Besides micro-/nanorods, which were previously reported for homopolymers, sphere and sheetlike structures were unexpectedly fabricated from block copolymers depending on the solvent quality, solvent exchange rates, and the entanglement of the polymer chains. In particular, the sheet structure, fabricated from poly(ethylene glycol)-b-polystyrene (PEG-b-PS), can be fixed by UV irradiation when photo-crosslinkable azide groups were introduced onto the polystyrene block. Surprisingly, we found that the fixed sheetlike structures show demulsification capability in tens of seconds, which may have great potential application in the separation of oil from emulsions.

"Bitter-Sweet" Polymeric Micelles Formed by Block Copolymers from Glucosamine and Cholic Acid.

Natural compounds glucosamine and cholic acid have been used to make acrylic monomers which are subsequently used to prepare amphiphilic block copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization. Despite the striking difference in polarity and solubility, three diblock copolymers consisting of glucosamine and cholic acid pendants with different hydrophilic and hydrophobic chain lengths have been synthesized without the use of protecting groups. They are shown to self-assemble into polymeric micelles with a "bitter" bile acid core and "sweet" sugar shell in aqueous solutions, as evidenced by dynamic light scattering and transmission electron microscopy. The critical micelle concentration varies with the hydrophobic/hydrophilic ratio, ranging from 0.62 to 1.31 mg/L. Longer chains of polymers induced the formation of larger micelles in range of 50-70 nm. These micelles can solubilize hydrophobic compounds such as Nile Red in aqueous solutions. Their loading capacity mainly depends upon the hydrophobic/hydrophilic ratio of the polymers, and may be also related to the length of the hydrophilic block. These polymeric micelles allowed for a 10-fold increase in the aqueous solubility of paclitaxel and showed no cytotoxicity below the concentration of 500 mg/L. Such properties make these polymeric micelles interesting reservoirs for hydrophobic molecules and drugs for biomedical applications.

Tunable Pickering Emulsions with Environmentally Responsive Hairy Silica Nanoparticles.

Surface modification of the nanoparticles using surface anchoring of amphiphilic polymers offers considerable scope for the design of a wide range of brush-coated hybrid nanoparticles with tunable surface wettability that may serve as new class of efficient Pickering emulsifiers. In the present study, we prepared mixed polymer brush-coated nanoparticles by grafting ABC miktoarm star terpolymers consisting of poly(ethylene glycol), polystyrene, and poly[(3-triisopropyloxysilyl)propyl methacrylate] (µ-PEG-b-PS-b-PIPSMA) on the surface of silica nanoparticles. The wettability of the as-prepared nanoparticles can be precisely tuned by a change of solvent or host-guest complexation. 1H NMR result confirmed that such wettability change is due to the reorganization of the polymer chain at the grafted layer. We show that this behavior can be used for stabilization and switching between water-in-oil (W/O) and oil-in-water (O/W) emulsions. For hairy particles initially dispersed in oil, W/O emulsions were always obtained with collapsed PEG chains and mobile PS chains at the grafted layer. However, initially dispersing the hairy particles in water resulted in O/W emulsions with collapsed PS chains and mobile PEG chains. When a good solvent for both PS and PEG blocks such as toluene was used, W/O emulsions were always obtained no matter where the hairy particles were dispersed. The wettability of the mixed polymer brush-coated silica particles can also be tuned by host-guest complexation between PEG block and α-CD. More importantly, our result showed that surprisingly the resultant mixed brush-coated hairy nanoparticles can be employed for the one-step production of O/W/O multiple emulsions that are not attainable from conventional Pickering emulsifiers. The functionalized hairy silica nanoparticles at the oil-water interface can be further linked together utilizing poly(acrylic acid) as the reversible linker to form supramolecular colloidosomes, which show pH-dependent release of cargo.

Facile Fabrication of Water Dispersible Latex Particles with Homogeneous or Chain-Segregated Surface from RAFT Polymerization Using a Mixture of Two Macromolecular Chain Transfer Agents.

Water dispersible latex particles with randomly mixed shells or chain segregated surface are synthesized from one-pot reversible addition-fragmentation chain transfer heterogeneous polymerization of benzyl methacrylate (BzMA) using a mixture of poly(glycerol monomethacrylate) (PGMA) and poly(2,3-bis(succinyloxy)propyl methacrylate) (PBSPMA) macromolecular chain transfer agents. In methanol, the two in situ synthesized PGMA-b-PBzMA and PBSPMA-b-PBzMA diblock copolymers coaggregate into spherical micelles, which contain PBzMA core and discrete PGMA and PBSPMA nanodomains on the shell. In contrast, in water-methanol mixture (V/V = 9/1), latex particles with homogeneous distribution of PGMA and PBSPMA polymer chains on the shell are obtained. The reasons leading to formation of latex particles with homogenous or chain-segregated surface are discussed, and polymerization kinetics and physical state of PBSPMA in methanol and water-methanol mixtures are ascribed. These polymeric micelles with patterned functional group on the surface are potentially important for application in supracolloidal hierarchical assemblies and catalysis.

One-step formation of w/o/w multiple emulsions stabilized by single amphiphilic block copolymers.

Multiple emulsions are complex polydispersed systems in which both oil-in-water (O/W) and water-in-oil (W/O) emulsion exists simultaneously. They are often prepared accroding to a two-step process and commonly stabilized using a combination of hydrophilic and hydrophobic surfactants. Recently, some reports have shown that multiple emulsions can also be produced through one-step method with simultaneous occurrence of catastrophic and transitional phase inversions. However, these reported multiple emulsions need surfactant blends and are usually described as transitory or temporary systems. Herein, we report a one-step phase inversion process to produce water-in-oil-in-water (W/O/W) multiple emulsions stabilized solely by a synthetic diblock copolymer. Unlike the use of small molecule surfactant combinations, block copolymer stabilized multiple emulsions are remarkably stable and show the ability to separately encapsulate both polar and nonpolar cargos. The importance of the conformation of the copolymer surfactant at the interfaces with regards to the stability of the multiple emulsions using the one-step method is discussed.

Chiral imprinting of diblock copolymer single-chain particles.

This Article reports the molecular imprinting of polymer single-chain particles that have a radius ∼3.7 nm. For this, the template L-phenylalanine anilide or L-ΦAA and a diblock copolymer PtBA-b-P(CEMA-r-CA) were used. Here, PtBA denotes poly(tert-butyl acrylate), and P(CEMA-r-CA) denotes a random block consisting of cinnamoyloxyethyl methacrylate (CEMA) and carboxyl-bearing (CA) units. In CHCl(3)/cyclohexane (CHX) with 64 vol % of CHX or at f(CHX) = 64%, a block-selective solvent for PtBA, PtBA-b-P(CEMA-r-CA) formed spherical micelles. The core consisted of the insoluble P(CEMA-r-CA) block and L-ΦAA, which complexed with the CA groups. Pumping slowly this micellar solution into stirred CHCl(3)/(CHX) at f(CHX) = 64% triggered micelle dissociation into single-chain micelles, which comprised presumably a solubilized PtBA tail and a collapsed P(CEMA-r-CA)/L-ΦAA head. Because the solvent reservoir was under constant UV irradiation, the photo-cross-linkable units in the P(CEMA-r-CA) head cross-linked, and the single-chain micelles were converted into cross-linked single-chain micelles or tadpoles. Synchronizing the micelle addition and photoreaction rates allowed the preparation, from this protocol, of essentially pure tadpoles at high final polymer concentrations. Imprinted tadpoles were procured after L-ΦAA was extracted from the tadpole heads. Under optimized conditions, the produced imprinted tadpoles had exceptionally high binding capacity and high selectivity for L-ΦAA. In addition, the rates of L-ΦAA release from and rebinding by the particles were high.

Water-dispersible superparamagnetic microspheres adorned with two types of surface chains.

Water-dispersible superparamagnetic polymer/γ-Fe(2)O(3) composite microspheres adorned with two types of surface polymer chains are prepared and characterized. To prepare these spheres, we first synthesize uniform γ-Fe(2)O(3) nanoparticles that are covered by poly(2-cinnamoyloxyethyl methacrylate)-block-poly(acrylic acid) (PCEMA-b-PAA). These nanoparticles are then mixed with a PCEMA homopolymer in CHCl(3) to form an oil phase. The oil phase is dispersed into water under vigorous stirring with the help of two diblock copolymer surfactants, PGMA-b-PCEMA and PSGMA-b-PCEMA. Here PGMA and PSGMA denote poly(glyceryl monomethacrylate) and succinated PGMA, respectively. Solid microspheres with cores composed of PCEMA and PCEMA-b-PAA-covered γ-Fe(2)O(3) nanoparticles are obtained after CHCl(3) evaporation and PCEMA photo-cross-linking. Under certain conditions, the coronal PGMA and PSGMA chains become segregated, thus producing surface bumps, ridges, and valleys. The PSGMA chains preferentially cover the protruding regions. The PSGMA carboxyl groups are used to immobilize bovine serum albumin (BSA). The immobilized BSA retains its activity and binds with anti-BSA. These spheres should be useful in immunoassays.

Slow relaxation mode in mixtures of water and organic molecules: supramolecular structures or nanobubbles?

Aqueous solutions of tetrahydrofuran, ethanol, urea, and alpha-cyclodextrin were studied by a combination of static and dynamic laser light scattering (LLS). In textbooks, these small organic molecules are soluble in water so that there should be no observable large structures or density fluctuation in either static or dynamic LLS. However, a slow mode has been consistently observed in these aqueous solutions in dynamic LLS. Such a slow mode was previously attributed to some large complexes or supramolecular structures formed between water and these small organic molecules. Our current study reveals that it is actually due to the existence of small bubbles ( approximately 100 nm in diameter) formed inside these solutions. Our direct evidence comes from the fact that it can be removed by repeated filtration and regenerated by air injection. Our results also indicate that the formation of such nanobubbles in small organic molecule aqueous solutions is a universal phenomenon. Such formed nanobubbles are rather stable. The measurement of isothermal compressibility confirms the existence of a low density microphase, presumably nanobubbles, in these aqueous solutions. Using a proposed structural model, that is, each bubble is stabilized by small organic molecules adsorbed at the gas/water interface, we have, for the first time, estimated the pressure inside these nanobubbles.