Disruption of Communication: Recent Advances in Antibiofilm Materials with Anti-Quorum Sensing Properties.

Biofilm contamination presents a significant threat to public health, the food industry, and aquatic/marine-related applications. In recent decades, although various methods have emerged to combat biofilm contamination, the intricate and persistent nature of biofilms makes complete eradication challenging. Therefore, innovative alternative solutions are imperative for addressing biofilm formation. Instead of solely focusing on the eradication of mature biofilms, strategically advantageous measures involve the delay or prevention of biofilm formation on surfaces. Quorum sensing, a communication system enabling bacteria to coordinate their behavior based on population density, plays a pivotal role in biofilm formation for numerous microbial species. Materials possessing antibiofilm properties that target quorum sensing have gained considerable attention for their potential to prevent biofilm formation. This Review consolidates recent research progress on the utilization of materials with antiquorum sensing properties for combating biofilm formation. These materials can be categorized into three distinct types: (i) antibiofilm nanomaterials, (ii) antibiofilm surfaces, and (iii) antibiofilm hydrogels with antiquorum sensing capabilities. Finally, the Review concludes with a brief discussion of current challenges and outlines potential avenues for future research.

Enhanced Intracellular Delivery and Cell Harvest Using a Candle Soot-Based Photothermal Platform with Dual-Stimulus Responsiveness.

Intracellular delivery of bioactive macromolecules and functional materials plays a crucial role in fundamental biological research and clinical applications. Nondestructive and efficient harvesting of engineered cells is also required for some specific applications. In this work, we develop a multifunctional platform based on candle soot modified with copolymer brushes containing temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and sugar-responsive phenylboronic acid (PBA) components. This platform possesses a high cell adhesion capacity due to the inherent hierarchical structure of candle soot and the formation of boronate ester bonds between the PBA groups and glycoproteins on the cell membrane. Under the irradiation of a near-infrared laser, the excellent light-to-heat conversion ability of candle soot enables the highly efficient delivery of macromolecules into diverse cells (including hard-to-transfect cells) attached to the surface via a photothermal-poration mechanism. Owing to the temperature-responsive properties of PNIPAAm and the sugar-responsive properties of PBA, the engineered cells could be harvested nondestructively from the platform by a mild treatment using a cold fructose solution. A proof-of-concept experiment demonstrates that fibroblasts attached to the surface could be transfected by a functional plasmid encoding basic fibroblast growth factor and then harvested efficiently and recultured with improved proliferation and migration ability. The whole delivery-harvesting process required less than 1 h, allowing the cells to be engineered without compromising their viability. This platform thus provides a widely applicable method for both the intracellular delivery of diverse macromolecules efficiently as well as harvesting engineered cells simply and safely, holding great potential for biomedical applications.

Functionalized ZnMnFe2O4-PEG-FA nanoenzymes integrating diagnosis and therapy for targeting hepatic carcinoma guided by multi-modality imaging.

With its insidious onset and atypical early symptoms, hepatic carcinoma is one of the most common and malignant tumors in the world. Therefore, it is necessary to actively pursue efficient diagnostic and treatment modalities for this malignancy. Photothermal therapy (PTT) is a non-invasive treatment technique that can generate high temperatures locally to induce tumor cell death, but its effectiveness is limited by the tissue-penetration depth of infrared light. Enzyme-catalyzed therapy promotes the production of toxic hydroxyl groups (˙OH) from hydrogen peroxide in tumor cells in situ, but its efficacy is also affected by the catalytic efficiency of ˙OH. Thus, given the complexity of tumors, multimodal therapy is critical for cancer treatment. Herein, we report a novel biomimetic nanoparticle (NP) platform (ZnMnFe2O4-PEG-FA) that enables combined PTT and nanozyme-catalyzed therapy. Due to the excellent photothermal effect of ZnMnFe2O4-PEG-FA, these NPs can reach an ideal temperature and damage tumor cells under lower near-infrared laser power irradiation, while exhibiting enhanced catalytic ability, largely alleviating the limitations of conventional PTT and catalytic therapy. Hence, the combination of these two treatments can provide significantly greater cytotoxicity. Additionally, ZnMnFe2O4-PEG-FA NPs have excellent photoacoustic imaging and magnetic resonance imaging capabilities, which enable monitoring and can guide cancer treatment. Therefore, ZnMnFe2O4-PEG-FA NPs integrate the diagnosis and treatment of tumors. Hence, this study provides a potential model of combined cancer diagnosis and treatment, which could be applied as a multimodal antitumor strategy in clinical settings in the future.

A Photothermal Nanoplatform with Sugar-Triggered Cleaning Ability for High-Efficiency Intracellular Delivery.

Intracellular delivery of functional molecules is of great importance in various biomedical and biotechnology applications. Recently, nanoparticle-based photothermal poration has attracted increasing attention because it provided a facile and efficient method to permeabilize cells transiently, facilitating the entry of exogenous molecules into cells. However, this method still has some safety concerns associated with the nanoparticles that bind to the cell membranes or enter the cells. Herein, a nanoplatform with both photothermal property and sugar-triggered cleaning ability for intracellular delivery is developed based on phenylboronic acid (PBA) functionalized porous magnetic nanoparticles (named as M-PBA). The M-PBA particles could bind to the target cells effectively through the specific interactions between PBA groups and the cis-diol containing components on the cell membrane. During a short-term near-infrared irradiation, the bound particles convert absorbed light energy to heat, enabling high-efficiency delivery of various exogenous molecules into the target cells via a photothermal poration mechanism. After delivery, the bound particles could be easily "cleaned" from the cell surface via mild sugar-treatment and collected by a magnet, avoiding the possible side effects caused by the entrance of particles or their fragments. The delivery and cleaning process is short and effective without compromising the viability and proliferation ability of the cells with delivered molecules, suggesting that the M-PBA particles could be used as promising intracellular delivery agents with a unique combination of efficiency, safety, and flexibility.

Photothermal scaffolds/surfaces for regulation of cell behaviors.

Regulation of cell behaviors and even cell fates is of great significance in diverse biomedical applications such as cancer treatment, cell-based therapy, and tissue engineering. During the past decades, diverse methods have been developed to regulate cell behaviors such as applying external stimuli, delivering exogenous molecules into cell interior and changing the physicochemical properties of the substrates where cells adhere. Photothermal scaffolds/surfaces refer to a kind of materials embedded or coated with photothermal agents that can absorb light with proper wavelength (usually in near infrared region) and convert light energy to heat; the generated heat shows great potential for regulation of cell behaviors in different ways. In the current review, we summarize the recent research progress, especially over the past decade, of using photothermal scaffolds/surfaces to regulate cell behaviors, which could be further categorized into three types: (i) killing the tumor cells via hyperthermia or thermal ablation, (ii) engineering cells by intracellular delivery of exogenous molecules via photothermal poration of cell membranes, and (iii) releasing a single cell or an intact cell sheet via modulation of surface physicochemical properties in response to heat. In the end, challenges and perspectives in these areas are commented.

Surface-Mediated Intracellular Delivery by Physical Membrane Disruption.

Effective and nondestructive intracellular delivery of exogenous molecules and other functional materials into living cells is of importance for diverse biological fundamental research and therapeutic applications, such as gene editing and cell-based therapies. However, for most exogenous molecules, the cell plasma membrane is effectively impermeable and thus remains the greatest barrier to intracellular delivery. In recent years, methods based on surface-mediated physical membrane disruption have attracted considerable attention. These methods exploit the physical properties of the surface to transiently increase the membrane permeability of cells come in contact thereto, thereby facilitating the efficient intracellular delivery of molecules regardless of molecule or target cell type. In this Review, we focus on recent progress, particularly over the past decade, on these surface-mediated membrane disruption-based delivery systems. According to the membrane disruption mechanism, three categories can be recognized: (i) mechanical penetration, (ii) electroporation, and (iii) photothermal poration. Each of these is discussed in turn and a brief perspective on future developments in this promising area is presented.

Photothermally Activated Electrospun Nanofiber Mats for High-Efficiency Surface-Mediated Gene Transfection.

Although electrospun nanofibers have been used to deliver functional genes into cells attached to the surface of the nanofibers, the controllable release of genes from nanofibers and the subsequent gene transfection with high efficiency remain challenging. Herein, photothermally activated electrospun hybrid nanofibers are developed for high-efficiency surface-mediated gene transfection. Nanofibers with a core-sheath structure are fabricated using coaxial electrospinning. Plasmid DNA (pDNA) encoding basic fibroblast growth factor is encapsulated in the fiber core, and gold nanorods with photothermal properties are embedded in the fiber sheath composed of poly(l-lactic acid) and gelatin. The nanofiber mats show excellent and controllable photothermal response under near-infrared irradiation. The permeability of the nanofibers is thereby enhanced to allow the rapid release of pDNA. In addition, transient holes are formed in the membranes of NIH-3T3 fibroblasts attached to the mat, thus facilitating delivery and transfection with pDNA and leading to increased proliferation and migration of the transfected cells in vitro. This work offers a facile and reliable method for the regulation of cell function and cell behavior via localized gene transfection, showing great potential for application in tissue engineering and cell-based therapy.

Multistimulus Responsive Biointerfaces with Switchable Bioadhesion and Surface Functions.

Stimuli-responsive biointerfaces can serve as dynamic tools for modulation of biointerfacial interactions. Considering the complexity of biological environments, surfaces with multistimulus responsive switchable bioactivity are of great interest. In the work reported herein, a multistimulus responsive biointerface with on-off switchable bioadhesion (protein adsorption, bacterial adhesion, and cell adhesion) and surface functions in response to change in temperature, pH, or sugar content is developed. This surface is based on a silicon modified with a copolymer containing a thermoresponsive component (poly(N-isopropylacrylamide)) and a component, phenylboronic acid, that can form pH-responsive and sugar-responsive dynamic boronate ester bonds with diol-containing molecules. It is shown that biointeractions including protein adsorption and release, bacteria and cell attachment and detachment on this surface can be regulated by changing temperature, pH, and sugar content of the medium, either individually or all three simultaneously. Furthermore, this surface can switch between two different functions, namely between killing and releasing bacteria, by introduction of a diol-containing biocidal compound. Compared to switchable surfaces that are responsive to only one stimulus, our multistimulus responsive surface is better adapted to respond to the multifunctional complexities of the biological environment and thus has potential for use in numerous biomedical and biotechnology applications.

Smart, Photothermally Activated, Antibacterial Surfaces with Thermally Triggered Bacteria-Releasing Properties.

The development of effective antibacterial surfaces to prevent the attachment of pathogenic bacteria and subsequent bacterial colonization and biofilm formation is critically important for medical devices and public hygiene products. In the work reported herein, a smart antibacterial hybrid film based on tannic acid/Fe3+ ion (TA/Fe) complex and poly(N-isopropylacrylamide) (PNIPAAm) is deposited on diverse substrates. This surface is shown to have bacteria-killing and bacteria-releasing properties based on, respectively, near-infrared photothermal activation and subsequent cooling. The TA/Fe complex has three roles in this system: (i) as a universal adhesive "anchor" for surface modification, (ii) as a high-efficiency photothermal agent for ablation of attached bacteria (including multidrug resistant bacteria), and (iii) as a robust linker for immobilization of NH2-terminated PNIPAAm via either Michael addition or Schiff base formation. Moreover, because of the thermoresponsive properties of the immobilized PNIPAAm, almost all of the killed bacteria and other debris can be removed from the surface simply by lowering the temperature. It is shown that this hybrid film can maintain good antibacterial performance after being used for multiple "kill-and-release" cycles and can be applied to various substrates regardless of surface chemistry or topography, thus providing a broadly applicable, simple, and reliable solution to the problems associated with surface-attached bacteria in various healthcare applications.

Two-in-One Platform for High-Efficiency Intracellular Delivery and Cell Harvest: When a Photothermal Agent Meets a Thermoresponsive Polymer.

Efficient intracellular delivery of exogenous macromolecules is a key operation in biological research and for clinical applications. Moreover, under particular in vitro or ex vivo conditions, harvesting the engineered cells that maintain good viability is also important. However, none of the methods currently available is truly satisfactory in all respects. Herein, a "two-in-one" platform based on a polydopamine/poly( N-isopropylacrylamide) (PDA/PNIPAAm) hybrid film is developed, showing high efficiency in both cargo delivery and cell harvest without compromising cell viability. Due to the strong photothermal effect of PDA in response to near-infrared irradiation, this film can deliver diverse molecules to a number of cell types (including three hard-to-transfect cells) with an efficiency of ∼99% via membrane-disruption mechanism. Moreover, due to the thermoresponsive properties of PNIPAAm, the cells are harvested from the film without compromising viability by simply decreasing the temperature. A proof-of-concept experiment demonstrates that, using this platform, "recalcitrant" endothelial cells can be transfected by the functional ZNF580 gene and the harvested transfected cells can be recultured with high retention of viability and improved migration. In general, this "two-in-one" platform provides a reliable, universally applicable approach for both intracellular delivery and cell harvest in a highly efficient and nondestructive way, with great potential for use in a wide range of biomedical applications.

Sweet Switch: Sugar-Responsive Bioactive Surfaces Based on Dynamic Covalent Bonding.

Smart bioactive surfaces that can modulate interactions with biological systems are of great interest. In this work, a surface with switchable bioactivity in response to sugars has been developed. It is based on dynamic covalent bonding between phenylboronic acid (PBA) and secondary hydroxyls on the "wide" rim of ß-cyclodextrin (ß-CD). The system reported consists of gold surface modified with PBA-containing polymer brushes and a series of functional ß-CD derivatives conjugated to diverse bioactive ligands (CD-X). CD-X molecules are attached to the surface to give specified bioactivity such as capture of a specific protein or killing of attached bacteria. Subsequent treatment with cis-diol containing biomolecules having high affinity for PBA (e.g. fructose) leads to the release of CD-X together with the captured proteins, killed bacteria, and so forth from the surface. The surface bioactivity is thereby "turned off". Effectively, this constitutes an on-off bioactivity switch in a mild and noninvasive way, which has the potential in the design of dynamic bioactive surfaces for biomedical applications.

Regenerable smart antibacterial surfaces: full removal of killed bacteria via a sequential degradable layer.

Conventional antibacterial surfaces are becoming less effective due to the emergence of multidrug resistant bacteria; in addition, difficulties related to the accumulation of killed bacteria are generally encountered. To circumvent these problems, in the present work, an antibiotic-free and regenerable antibacterial hybrid film with both photothermal bactericidal activity and bacteria-releasing properties was fabricated on diverse substrates by sequential deposition of a gold nanoparticle layer (GNPL) and a phase-transitioned lysozyme film (PTLF). Due to the photothermal effect of the GNPL, the hybrid film was able to kill >99% of attached bacteria under near-infrared laser irradiation in 5 min. Moreover, the topmost PTLF layer could be degraded and detached from the surface by immersion in vitamin C solution for a short period, leading to removal of the killed bacteria and surface regeneration. The surface could be used and regenerated in this way through multiple cycles for long-term effective performance. The surface fabrication process is simple and environmentally friendly, and can be applied to diverse materials. These hybrid films thus offer a viable alternative for the killing and removal of adherent bacteria (particularly multidrug resistant bacteria) on the surfaces of medical devices for in vitro applications.

Self-assembled proteinaceous wound dressings attenuate secondary trauma and improve wound healing in vivo.

A new type of wound dressing that can be easily peeled from a wound during frequent changes is essential in clinical applications to reduce secondary trauma and relieve the pain suffered by patients. Here, we discover that a phase-transitioned lysozyme nanofilm (PTLF) composed of self-assembled protein nanoparticles with an amyloid-like internal structure can be disassembled and detached from a substrate surface under the stimulus of vitamin C solution. Accordingly, stimuli-responsive gauze coated with this phase-transitioned lysozyme nanofilm (PTLF@gauze) was developed. This novel wound dressing, PLTF@gauze, was fabricated through a simple, universal and environmentally benign approach by immersing pristine gauze in the lysozyme phase transition aqueous solution for minutes. In comparison with pristine gauze, the PTLF@gauze can be peeled from a mouse wound with less strength, causing less secondary trauma. This is due to the disassembly and detachment of the PTLF from the gauze in the presence of vitamin C, which is entirely different from normal low-adherent wound dressings based on anti-fouling. Additionally, the PTLF@gauze was shown to accelerate wound closure using a murine wound healing model owing to the anti-infection properties of PTLF. This work thus provides an effective surface modification method for medical devices and suggests the great potential applications of self-assembled proteinaceous coatings in wound care.

A supramolecular approach for versatile biofunctionalization of magnetic nanoparticles.

A convenient and versatile approach for biofunctionalization of magnetic nanoparticles (MNPs) was developed based on supramolecular host-guest interaction. Adamantane groups were introduced on the surface of MNPs for further incorporation of specific biofunctional ß-cyclodextrin derivatives, endowing MNPs with the desired bioactivity (e.g. biorecognition capability and biocidal activity).

Intracellular Delivery Platform for "Recalcitrant" Cells: When Polymeric Carrier Marries Photoporation.

The intracellular delivery of exogenous macromolecules is of great interest for both fundamental biological research and clinical applications. Although traditional delivery systems based on either carrier mediation or membrane disruption have some advantages; however, they are generally limited with respect to delivery efficiency and cytotoxicity. Herein, a collaborative intracellular delivery platform with excellent comprehensive performance is developed using polyethylenimine of low molecular weight (LPEI) as a gene carrier in conjunction with a gold nanoparticle layer (GNPL) acting as a photoporation agent. In this system, the LPEI protects the plasmid DNA (pDNA) to avoid possible nuclease degradation, and the GNPL improves the delivery efficiency of the LPEI/pDNA complex to the cells. The collaboration of LPEI and GNPL is shown to give significantly higher transfection efficiencies for hard-to-transfect cells (88.5 ± 9.2% for mouse embryonic fibroblasts, 94.0 ± 6.3% for human umbilical vein endothelial cells) compared to existing techniques without compromising cell viability.

A supramolecular bioactive surface for specific binding of protein.

Bioactive surfaces with immobilized bioactive molecules aimed specifically at promoting or supporting particular interactions are of great interest for application of biosensors and biological detection. In this work, we fabricated a supramolecular bioactive surface with specific protein binding capability using two noncovalent interactions as the driving forces. The substrates were first layer-by-layer (LbL) deposited with a multilayered polyelectrolyte film containing "guest" adamantane groups via electrostatic interactions, followed by incorporation of "host" ß-cyclodextrin derivatives bearing seven biotin units (CD-B) into the films via host-guest interactions. The results of fluorescence microscopy and quartz crystal microbalance measurement demonstrated that these surfaces exhibited high binding capacity and high selectivity for avidin due to the high density of biotin residues. Moreover, since host-guest interactions are inherently reversible, the avidin-CD-B complex is easily released by treatment with the sodium dodecyl sulfate, and the "regenerated" surfaces, after re-introducing fresh CD-B, can be used repeatedly for avidin binding. Given the generality and versatility of this approach, it may pave a way for development of re-usable biosensors for the detection and measurement of specific proteins.

Supramolecular Platform with Switchable Multivalent Affinity: Photo-Reversible Capture and Release of Bacteria.

Surfaces having dynamic control of interactions at the biological system-material interface are of great scientific and technological interest. In this work, a supramolecular platform with switchable multivalent affinity was developed to efficiently capture bacteria and on-demand release captured bacteria in response to irradiation with light of different wavelengths. The system consists of a photoresponsive self-assembled monolayer containing azobenzene (Azo) groups as guest and ß-cyclodextrin (ß-CD)-mannose (CD-M) conjugates as host with each CD-M containing seven mannose units to display localized multivalent carbohydrates. Taking the advantage of multivalent effect of CD-M, this system exhibited high capacity and specificity for the capture of mannose-specific type 1-fimbriated bacteria. Moreover, ultraviolet (UV) light irradiation caused isomerization of the Azo groups from trans-form to cis-form, resulting in the dissociation of the host-guest Azo/CD-M inclusion complexes and localized release of the captured bacteria. The capture and release process could be repeated for multiple cycles, suggesting good reproducibility. This platform provides the basis for development of reusable biosensors and diagnostic devices for the detection and measurement of bacteria and exhibits great potential for use as a standard protocol for the on-demand switching of surface functionalities.

A reusable supramolecular platform for the specific capture and release of proteins and bacteria.

In this work, a reusable supramolecular platform for the specific capture and release of proteins and bacteria was developed. Multilayered polyelectrolyte films containing "guest" moieties were first fabricated using the layer-by-layer (LbL) deposition of poly(allylamine hydrochloride) and poly(acrylic acid-co-1-adamantan-1-ylmethyl acrylate), followed by the incorporation of ß-cyclodextrin (ß-CD) derivatives modified with mannose (CD-M) as "host" molecules with protein (lectin) binding properties. This platform combines three different non-covalent interactions: electrostatic interactions for the LbL deposition of multilayered films, host-guest inclusion for the incorporation of ß-CD-conjugated ligands, and carbohydrate-protein affinity recognition for the capture of specific proteins and bacteria. For the mannose system investigated, the capture of Concanavalin A (ConA) and type I fimbriated Escherichia coli was demonstrated. Moreover, due to the inherent reversibility of host-guest interactions, the captured proteins and bacteria could be easily released from the surface by incubation with sodium dodecyl sulfate, and the renewed "guest" surface could be treated with the CD-M "host" to regenerate the ConA and E. coli-binding surface. This "use-regenerate" cycle could be repeated multiple times without significant loss of bioactivity. Given the generality and versatility of this approach, it may provide the basis for the development of re-usable biosensors and diagnostic devices for the detection and measurement of proteins and bacteria.

Multifunctional and Regenerable Antibacterial Surfaces Fabricated by a Universal Strategy.

Development of a versatile strategy for antibacterial surfaces is of great scientific interest and practical significance. However, few methods can be used to fabricate antibacterial surfaces on substrates of different chemistries and structures. In addition, traditional antibacterial surfaces may suffer problems related to the attached dead bacteria. Herein, antibacterial surfaces with multifunctionality and regenerability are fabricated by a universal strategy. Various substrates are first deposited with multilayered films containing guest moieties, which can be further used to incorporate biocidal host molecules, ß-cyclodextrin (ß-CD) derivatives modified with quaternary ammonium salt groups (CD-QAS). The resulting surfaces exhibit strong biocidal activity to kill more than 95% of attached pathogenic bacteria. Notably, almost all the dead bacteria can be easily removed from the surfaces by simple immersion in sodium dodecyl sulfate, and the regenerated surfaces can be treated with new CD-QAS for continued use. Moreover, when another functional ß-CD derivative molecule is co-incorporated together with CD-QAS, the surfaces exhibit both functions simultaneously, and neither specific biofunction and antibacterial activity is compromised by the presence of the other. These results thus present a promising way to fabricate multifunctional and regenerable antibacterial surfaces on diverse materials and devices in the biomedical fields.