Nitrite reductase-mimicking catalysis temporally regulating nitric oxide concentration gradient adaptive for antibacterial therapy.

The unique bacterial infection microenvironment (IME) usually requires complicated design of nanomaterials to adapt to IME for enhancing antibacterial therapy. Here, an alternative IME adaptative nitrite reductase-mimicking nanozyme is constructed by in situ growth of ultrasmall copper sulfide clusters on the surface of a nanofibrillar lysozyme assembly (NFLA/CuS NHs), which can temporally regulate nitric oxide (NO) gradient concentration to kill bacteria initially and promote tissue regeneration subsequently. Benefiting from a copper nitrite reductase (CuNIR)-inspired structure with CuS cluster as active center and NFLA as skeleton, NFLA/CuS NHs efficiently boost the catalytic reduction of nitrite to NO. The inherent supramolecular fibrillar networks displays excellent bacterial capture capability, facilitating initial high-concentration NO attacks on the bacteria. The subsequent catalytic release of low-concentration NO by NFLA/CuS NHs-mediated nitrite reduction remarkably promotes cell migration and angiogenesis. This work paves the way for dynamically eliminating MDR bacterial infection and promoting tissue regeneration in a simple and smart way through CuNIR-mimicking catalysis.

Identification and prognostic analysis of ferroptosis­related gene HSPA5 to predict the progression of lung squamous cell carcinoma.

Ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, is implicated in the development and therapeutic responses of cancer. However, the role of ferroptosis-related gene profiles in lung squamous cell carcinoma (LSCC) remains largely unknown. The present study aimed to identify the prognostic roles of ferroptosis-related genes in LSCC. Sequencing data from the Cancer Genome Atlas were analyzed and ferroptosis-related gene expression between tumor and para-tumor tissue was identified. The prognostic role of these genes was also assessed using Kaplan-Meier analyses and univariate and multivariate Cox proportional hazards regression model analyses. Immunological correlation, tumor stemness, drug sensitivity and the transcriptional differences of heat shock protein (HSP)A5 in LSCC were also analyzed. Thereafter, the expression of HSPA5 in 100 patients with metastatic LSCC was evaluated using immunohistochemistry (IHC) and the clinical significance of these markers with different risk factors was assessed. Of the 22 ferroptosis-related genes, the expression of HSPA5, HSPB1, glutathione peroxidase 4, Fanconi anemia complementation group D2, CDGSH iron sulfur domain 1, farnesyl-diphosphate farnesyltransferase 1, nuclear factor erythroid 2 like 2, solute carrier (SLC)1A5, ribosomal protein L8, nuclear receptor coactivator 4, transferrin receptor and SLC7A11 was significantly increased in LSCC compared with adjacent tissues. However, only high expression of HSPA5 was able to predict progression-free survival (PFS) and disease-free survival in LSCC. Although HSPA5 was also significantly elevated in patients with lung adenocarcinoma, HSPA5 expression did not predict the prognosis of patients with lung adenocarcinoma. Of note, a higher expression of HSPA5 was related to higher responses to chemotherapy but not to immunotherapy. In addition, HSPA5 expression was positively correlated with 'ferroptosis', 'cellular responses to hypoxia', 'tumor proliferation signature', 'G2M checkpoint', 'MYC targets' and 'TGFB'. IHC analysis also demonstrated that a high expression of HSPA5 in patients with metastatic LSCC in the study cohort was associated with shorter PFS and overall survival. In conclusion, the present study demonstrated that the expression of the ferroptosis-related gene HSPA5 may be a negative prognostic marker for LSCC.

Iron decoration in binary graphene oxide and copper iron sulfide nanocomposites boosting catalytic antibacterial activity in acidic microenvironment against antimicrobial resistance.

The strong antimicrobial resistance (AMR) of multidrug-resistant (MDR) bacteria and biofilm, especially the biofilm with extracellular polymeric substance (EPS) protection and persister cells, not only renders antibiotics ineffective but also causes chronic infections and makes the infectious tissue difficult to repair. Considering the acidic properties of bacterial infection microenvironment and biofilm, herein, a binary graphene oxide and copper iron sulfide nanocomposite (GO/CuFeSx NC) is synthesized by a surfactant free strategy and utilized as an alternative smart nanozyme to fight against the MDR bacteria and biofilm. For the GO/CuFeSx NC, the iron decoration facilitates the well distribution of bimetallic CuFeSx NPs on the GO surfaces compared to monometallic CuS NPs, providing synergistically enhanced peroxidase (POD)-like activity in acidic medium (pH 4 âˆ¼ 5) and intrinsic strong near infrared (NIR) light responsive photothermal activity, while the ultrathin and sharp structure of 2D GO nanosheet allows the GO/CuFeSx NC to strongly interact with the bacteria and biofilm, facilitating the catalytic and photothermal attacks on the bacterial surfaces. In addition, the GO in GO/CuFeSx NC exhibits a "Pseudo-Photo-Fenton" effect to promote the ROS generation. Therefore, the GO/CuFeSx NC can effectively kill bacteria and biofilm both in vitro and in vivo, finally eliminating the infections and accelerating the tissue repair when treating the biofilm-infected wound. This work paves a new way to the design of novel nanozyme for smart antibacterial therapy against antimicrobial resistance.

Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes.

Proteins and peptides can assemble into functional amyloid fibrils with distinct architectures. These amyloid fibrils can fulfil various biological functions in living organisms, and then be degraded. By incorporating an amyloidogenic segment and enzyme-cleavage segment together, we designed a peptide (enzyme-cleavage amyloid peptides (EAP))-based functional fibril which could be degraded specifically by gelatinase. To gain molecular insights into the assembly and degradation of EAP fibrils, we determined the atomic structure of the EAP fibril using cryo-electron microscopy. The amyloidogenic segment of EAP adopted a ß-strand conformation and mediated EAP-fibril formation mainly via steric zipper-like interactions. The enzyme-cleavage segment was partially involved in self-assembly, but also exhibited high flexibility in the fibril structure, with accessibility to gelatinase binding and degradation. Moreover, we applied the EAP fibril as a tunable scaffold for developing degradable self-assembled antimicrobial fibrils (SANs) by integrating melittin and EAP together. SANs exhibited superior activity for killing bacteria, and significantly improved the stability and biocompatibility of melittin. SANs were eliminated automatically by the gelatinase secreted from targeted bacteria. Our work provides a new strategy for rational design of functional fibrils with a feedback regulatory loop for optimizing the biocompatibility and biosafety of designed fibrils. Our work may aid further developments of "smart" peptide-based biomaterials for biomedical applications.

Amyloid-like nanofibrous network confined and aligned ultrafine bimetallic nanozymes for smart antibacterial therapy.

Nanozyme-based antibacterial therapy (NABT) has emerged as a promising strategy to combat bacterial antimicrobial resistance. Engineering the noble metal nanozymes with strong bacterial capture and high catalytic activity for enhanced NABT is highly anticipated but still challenged. Herein, we developed hybrid nanozymes by engineering ultrafine bimetallic Au/Cu nanoparticles confined on the lysozyme amyloid-like nanofibrous networks (LNF). The introduction of copper in the nanozymes facilitates the H2O2 adsorption and reduces the energy barrier for activating the H2O2 decomposition to form •OH, meanwhile displaying the significantly enhanced POD-like activity under NIR irradiation. Taking advantage of the inherent supramolecular networks inspired from human defensin 6-trapping bacteria mechanism, the hybrid nanozymes effectively capture the bacteria and allow the catalytic attack around the bacterial surfaces to improve the antibacterial efficiency. Finally, the as-prepared nanozymes exhibit the preeminent bactericidal efficacy against bacteria, especially for drug-resistant bacteria both in vitro and in vivo, and the effect on wound healing.

Silk fibroin-based piezoelectric nanofibrous scaffolds for rapid wound healing.

Piezoelectric polymer nanofibers are attracting increasing attention in the stimulation of cell growth and proliferation in tissue engineering and wound healing applications. However, their intrinsic non-biodegradability in vivo hinders widespread applications in the biological fields. Herein, we designed, synthesized and characterized composite materials of silk fibroin (SF)/LiNbO3 (LN) nanoparticles/MWCNTs by electrospinning technology, which displayed good biocompatibility and comparable piezoelectric properties with an output current of up to 15 nA and output voltage of up to 0.6 V under pressure stimulation, remaining stable after 200 cycles of pressure release without significant decay. Meanwhile, the mechanical properties of the LN/CNTs/SF-nanofiber scaffolds (SF-NFSs) are also enhanced, with a tensile strength reaching 12.84 MPa and an elongation at break reaching 80.07%. Importantly, in vitro cell proliferation experiments showed that the LN/CNTs/SF-NFSs promoted cell proliferation at a rate of 43%. Accordingly, the mouse wound healing experiments further indicated that they could accelerate the healing of skin wounds in mice that were continuously moving. Therefore, SF-based piezoelectric nanofibrous scaffolds exhibit potential for use in rapid wound healing and this sheds light on smart treatment for tissue engineering in biomedicine.

Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections.

Nanozymes are considered to represent a new era of antibacterial agents, while their antibacterial efficiency is limited by the increasing tissue depth of infection. To address this issue, here, we report a copper and silk fibroin (Cu-SF) complex strategy to synthesize alternative copper single-atom nanozymes (SAzymes) with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets (CuN x -CNS) and tunable N coordination numbers in the CuN x sites (x = 2 or 4). The CuN x -CNS SAzymes inherently possess triple peroxidase (POD)-, catalase (CAT)-, and oxidase (OXD)-like activities, facilitating the conversion of H2O2 and O2 into reactive oxygen species (ROS) through parallel POD- and OXD-like or cascaded CAT- and OXD-like reactions. Compared to CuN2-CNS, tailoring the N coordination number from 2 to 4 endows the SAzyme (CuN4-CNS) with higher multienzyme activities due to its superior electron structure and lower energy barrier. Meanwhile, CuN x -CNS display strong absorption in the second near-infrared (NIR-II) biowindow with deeper tissue penetration, offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues. The in vitro and in vivo results demonstrate that the optimal CuN4-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms, thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.

A hydrogel dressing with tunable critical temperature and photothermal modulating melittin release for multiply antibacterial treatment.

It is imperative to develop an antibiotic-free and long-term effective strategy for treating chronic wound infections due to the long-term utilization of antibiotics easily causing drug resistance. Herein, we fabricated a novel poly-N-isopropylacrylamide (PNIPAM)/polyacrylamide (PAM) coupling thermosensitive hydrogel integrating 1D lysozyme nanofiber doped with CuS nanoparticles (CuS/PP) and loading antibacterial peptide melittin (M) (CuS/PP-M) for combating chronic wound infection via photothermal modulating the release of melittin. For the CuS/PP-M hydrogel, the copolymerization of PNIPAM and PAM allows the lower critical solution temperature (LCST) higher than the body temperature, effectively hindering the spontaneous release of melittin when contacts the infected wound, while the integration of LNF/CuS nanofibers provides a stable photothermal treatment for triggering the release of melittin. As a result, the CuS/PP-M hydrogel exhibits synergistically enhanced effect on killing both Gram-positive and Gram-negative bacteria, which maintains more than 99 % bactericidal efficiency, even displays a long-term and multiply antibacterial performance by photothermal modulating melittin release. Moreover, the CuS/PP-M hydrogel presents both high antibacterial activity and excellent wound healing performance in the mouse wound model, thereby benefiting the chronic wound healing.

A bio-inspired versatile free-standing membrane for oral cavity microenvironmental monitoring and remineralization to prevent dental caries.

The fast monitoring of oral bacterial infection, bacterial clearance and repairing of enamel damage caused by dental caries relies on an effective way of monitoring, killing and repairing in situ, but presents a major challenge in oral healthcare. Herein, we developed a bio-inspired versatile free-standing membrane by filling TiO2 nanotube arrays with ß-sheet-rich silk fibroin and cleaving them from Ti foil, as inspired by nacre or enamel-like structures. The robust transparent membrane exhibited good mechanical properties, and could indicate acid-base microenvironment variation and the infection of S. mutans in a 5 min test by loading cyanidin cations in the membrane. Meanwhile, it can be used for photocatalysis and nanoreservoirs ascribed to TiO2 nanotubes, to kill and remove 99% of S. mutans bacteria under interval UV irradiation with low-power density, and load functional peptide to induce the remineralization on the etched-enamel for long-term treatment, tested in vitro and in vivo. The mechanical property of repaired enamel is improved in comparison. This bio-inspired constructed membrane would be applied in the prevention and treatment of oral cavity related diseases, such as enamel demineralization and dental caries, etc.

Boosting Photosynthetic H2O2 of Polymeric Carbon Nitride by Layer Configuration Regulation and Fluoride-Potassium Double-Site Modification.

Photocatalytic hydrogen peroxide (H2O2) production will become a burgeoning strategy for solar energy utilization by selective oxygen reduction reaction (ORR). Polymeric carbon nitride (PCN) shows relatively high two-electron ORR selectivity for H2O2 production but still limited low H2O2 production efficiency due to slow exciton dissociation. Herein, we constructed a heptazine/triazine layer stacked carbon nitride heterojunction with fluorine/potassium (F/K) dual sites (FKHTCN). The introduction of F/K not only can regulate layer components to enhance the charge separation efficiency but, more importantly, also optimize the adsorption of surface oxygen molecules and intermediate *OOH during H2O2 production. Consequently, FKHTCN efficiently improves the photocatalytic H2O2 production rate up to 3380.9 µmol h-1 g-1, nearly 15 times higher than that of traditional PCN. Moreover, a production-utilization cascade system was designed to explore their practical application in environmental remediation. This work lays out the importance of engineering a layer-stacked configuration and active sites for enhancing photocatalysis.

Cofactors-like peptide self-assembly exhibiting the enhanced catalytic activity in the peptide-metal nanocatalysts.

The peptide self-assembly would be expected to be as the assistance of metallic nanocatalysts to promote the catalytic reaction, attracting limited attention, but being highly anticipated. Herein, we proposed and verified an alternative strategy for enhancing the catalytic activity of the 4-nitrophenol reduction as a model reaction, by optimizing and constructing "cofactors" inspired amyloid peptide self-assembly applied in the peptide-metal nanocatalysts as the template due to the potential superiority of substrate binding. Amyloid peptide self-assembled membrane exhibited better enhanced catalytic activity, compared to peptide nanofibers as the template in the peptide-gold nanocatalysts. The optimized amyloid peptide was designated by molecular dynamic simulation to display the relative strongest interaction with specific substrate and the relative good template effect on the enhanced catalytic activity was also proved accordingly. This work may shed light on the future design and construction of novel enzyme mimics with dramatic enhanced catalytic activity by peptide assembly-metal nanocatalysts.

Apoptosis-like bacterial death modulated by photoactive hyperthermia nanomaterials and enhanced wound disinfection application.

Photothermal therapy (PTT) is considered as an efficient therapeutic strategy for wound disinfection. However, there is a dilemma that on the one hand, the high PTT temperature for killing bacteria (>58 °C) could cause serious injury to normal tissue, however, low-temperature results in unsatisfactory treatment efficiency. To settle the issue, we have proposed a novel approach to gently kill bacteria in an apoptosis-like mode via PTT, in which the bacteria can maintain intact membranes but cannot proliferate. This is different from the typical necrosis-like mode of bacterial cell death requiring higher temperatures. We found that PTT prefers to trigger the gradual efflux of Ca2+/Mg2+ ions from the bacterial intracellular content rather than directly destroy the outer membranes, but can cause the dynamic variation of the membrane surface micromorphology. Hence, the microbial viability of E. coli can be dynamically changed from the live state to an apoptosis-like state (45-55 °C), then to apoptosis/necrosis (ca. 58 °C), and finally to necrosis (>61 °C). Based on this strategy, we can kill bacteria through an apoptosis-like mode. Better healing efficacy of mice wounds was achieved at a PTT temperature of 50 °C as compared to that at 58 °C, which sheds light on the wound disinfection and healing applications in clinics with a mild PTT strategy.

A novel mixed matrix polysulfone membrane for enhanced ultrafiltration and photocatalytic self-cleaning performance.

Photocatalytic materials can be used as self-cleaning functional materials to alleviate the irreversible fouling of ultrafiltration membranes. In this work, the small size g-C3N4/Bi2MoO6 (SCB) blended polysulfone (PSF) ultrafiltration membranes was fabricated by hydrothermal and phase inversion methods. As a functional filler of ultrafiltration membranes, the small size g-C3N4 nanosheet decorated on the surface of Bi2MoO6 can enhance the photocatalytic performance for bovine serum albumin (BSA) degradation, and remove irreversible fouling under visible light irradiation. In addition, the introduction of SCB microspheres into PSF matrix obviously increased the porosity of ultrafiltration membranes. Therefore, the SCB-PSF ultrafiltration membranes displayed excellent antifouling performance (flux recovery ratio is 82.53%) and BSA rejection rates (94.77%). SCB-PSF also had high photocatalytic self-cleaning activity, indicating excellent application prospects in organic wastewater treatment.

Rationally constructing of a novel 2D/2D WO3/Pt/g-C3N4 Schottky-Ohmic junction towards efficient visible-light-driven photocatalytic hydrogen evolution and mechanism insight.

Effectively separating photo-generated charge carriers is usually important but difficult for the high-activity photocatalysis. Fabricating 2D/2D Schottky-Ohmic junction is more beneficial to the spatial separation and transfer of photo-induced charges at the interface of different components due to the matching of distinct two-dimension structure and band alignment, but the manipulation and mastery of junction type (Schottky-Ohmic junction and Z-scheme junction) and electronic structure is an arduous task for preparing satisfactory photocatalysts and investigating the PHE mechanism. In this work, the 2D/2D WO3/Pt/g-C3N4 (WPC) Schottky-Ohmic junction composite photocatalysts is formed via facile hydrothermal and photo-induced deposition method for employing to produce H2. The optimized WPC Schottky-Ohmic junction photocatalyst exhibits remarkable photocatalytic H2-release performance with ability to produce the amount of H2 reaches 1299.4 µmol upon exposure to visible light, which is about 1.2 and 11.5 times higher than that of WO3/g-C3N4/Pt (WCP) (1119.4 µmol) and pure CN (113.2 µmol)), respectively. This remarkable enhancement of photocatalytic performance is ascribed to: (i) Schottky-Ohmic junction can strikingly expedite spatial charge separation and elongate electron lifetime, (ii) the 2D/2D structure can shorten the charge transportation distance, (iii) Pt with rich electron density can stably adsorb H+. This work provides a successful paradigm for future fundamental research, and exquisitely designs ideal g-C3N4-based photocatalysts by simultaneously adjusting and optimizing material structure and electronic dynamics.

Characteristic of 523 COVID-19 in Henan Province and a Death Prediction Model.

Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP, and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0.907 (95% CI 0.831-0.983). Mixed model constructed with combination of age, demographics, symptoms, and laboratory findings at admission had better performance (p = 0.021) with a generalized AUC of 0.9852 (95% CI 0.961-1). We chose 0.441 as death prediction threshold (with 0.85 sensitivity and 0.987 specificity) and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients.

Bioclickable and mussel adhesive peptide mimics for engineering vascular stent surfaces.

Thrombogenic reaction, aggressive smooth muscle cell (SMC) proliferation, and sluggish endothelial cell (EC) migration onto bioinert metal vascular stents make poststenting reendothelialization a dilemma. Here, we report an easy to perform, biomimetic surface engineering strategy for multiple functionalization of metal vascular stents. We first design and graft a clickable mussel-inspired peptide onto the stent surface via mussel-inspired adhesion. Then, two vasoactive moieties [i.e., the nitric-oxide (NO)-generating organoselenium (SeCA) and the endothelial progenitor cell (EPC)-targeting peptide (TPS)] are clicked onto the grafted surfaces via bioorthogonal conjugation. We optimize the blood and vascular cell compatibilities of the grafted surfaces through changing the SeCA/TPS feeding ratios. At the optimal ratio of 2:2, the surface-engineered stents demonstrate superior inhibition of thrombosis and SMC migration and proliferation, promotion of EPC recruitment, adhesion, and proliferation, as well as prevention of in-stent restenosis (ISR). Overall, our biomimetic surface engineering strategy represents a promising solution to address clinical complications of cardiovascular stents and other blood-contacting metal materials.

Disassembling and degradation of amyloid protein aggregates based on gold nanoparticle-modified g-C3N4.

Amyloid protein misfolds, abnormally aggregates and accumulates into amyloid deposits which endanger tissue functions and are closely related to the pathogenesis of many diseases including Type 2 Diabetes Mellitus (T2DM). There are on-going efforts to find new methods or effective reagents to disassemble and eliminate the existing amyloid aggregates. Herein, we showed that a gold nanoparticle-modified quasi-2D nanomaterial, Au/g-C3N4, could efficiently degrade preformed amyloid aggregates. Furthermore, the scavenger experiment revealed this photodegradation effect was depended on the induced oxygen radicals, particularly hydroxyl radical. The new finding in this work could demonstrate that a gold nanoparticle-modified quasi-2D nanomaterial would have potential applications in the strategy design of the treatment of amyloid related diseases in future.

Self-Assembled Peptide Nanofibrils Designed to Release Membrane-Lysing Antimicrobial Peptides.

Membrane-disrupting antimicrobial peptides continue to attract increasing attention due to their potential to combat multidrug-resistant bacteria. However, some limitations are found in the success of clinical setting-based antimicrobial peptide agents, for instance, the poor stability of antimicrobial peptides in vivo and their short-term activity. Self-assembled peptide materials can improve the stability of antimicrobial peptides, but the biosafety of peptide-based materials is the main concern, although they are considered to be biocompatible, because some peptide aggregates would possibly induce protein misfolding, which could be related to amyloid-related diseases. Therefore, in this work, we designed two peptides and constructed peptide-based nanofibrils by self-assembly before its utilization. It is found that the fibrils could release the antimicrobial peptide by disassembly for microbial membrane lysis in the presence of bacteria. The designed peptide-based fibrils presented a good and long-term antimicrobial activity with bacterial membrane disruption and the efflux of calcium from bacteria. Furthermore, it could be used to construct hybrid macrofilms displaying low cytotoxicity, low hemolytic activity, and good biocompatibility. The innovative design strategy could be beneficial for the development of smart antimicrobial nanomaterials.

Deformation of stable and toxic hIAPP oligomers by liposomes with distinct nanomechanical features and reduced cytotoxicity.

Human islet amyloid polypeptide (hIAPP) oligomers are transient due to rapid aggregation rate in vitro, but play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we report an easy and robust method to generate toxic hIAPP oligomers, which are stable for at least 8 hours. The toxic hIAPP oligomers are quickly transformed from α-helix to ß-sheet by membrane phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes, exhibiting distinct nanomechanical features from the hIAPP oligomers or pristine fibrils. DOPC liposomes significantly block the cytotoxicity induced by the hIAPP oligomers, which has the potential for new treatment.

A Magnetic Dynamic Microbiointerface with Biofeedback Mechanism for Cancer Cell Capture and Release.

Dynamic biointerfaces with reversible surface bioactivities enable dynamic modulation of cell-material interactions, thus attracting great attention in biomedical science. Herein, we demonstrated a paradigm shift of dynamic biointerfaces from macroscopical substrates to micron-sized particles by reversible engineering of a phenylboronic acid (PBA)-functionalized magnetic microbead with mussel-inspired cancer cell-targeting peptide. Due to reversible catechol-boronate interactions between the peptides and microbeads, the micron-sized dynamic biointerface exhibited sugar-responsive cancer-targeting activity, showing the potential as a microplatform for magnetic and noninvasive isolation of cancer cells through natural biofeedback mechanism (e.g., human glycemic volatility). Our results demonstrated that the dynamic magnetic platform was capable of selective cancer cell capture (∼85%) and sugar-triggered release of them (>93%) in cell culture medium with high efficiency. More importantly, by using this platform, a decent number of target cells (∼23 on average) could be magnetically isolated and identified from artificial CTC blood samples (1 mL) spiked with 100 cancer cells. In view of the biomimetic nature, high capture efficiency, excellent selectivity, and superiority in cell separation and purification processes, the dynamic magnetic microplatform reported here would be a promising and general tool for rare cell detection and separation and cell-based disease diagnosis.