Layer‐By‐Layer Coating of Aminocellulose and Quorum Quenching Acylase on Silver Nanoparticles Synergistically Eradicate Bacteria and Their Biofilms

The emergence of antibiotic‐resistant bacteria and the failure of the existing antibacterial therapeutics call for development of novel treatment strategies. Furthermore, the formation of bacterial biofilms restricts drug penetration and efficiency, causing life‐threatening infections. Bacterial attachment and biofilm formation are regulated by the cell‐to‐cell communication phenomenon called quorum sensing (QS). In this work, antimicrobial silver nanoparticles (AgNPs) are decorated in a layer‐by‐layer fashion with the oppositely charged aminocellulose (AM) and acylase to generate hybrid nanoentities with enhanced antibacterial and antibiofilm activities as well as reduced cytotoxicity. Acylase, a quorum‐quenching enzyme that degrades the QS signals in the extracellular environment of bacteria, disrupts the bacterial QS process and together with the bactericidal AM synergistically lowers fourfold the minimum inhibitory concentration of the AgNPs templates toward Gram‐negative Pseudomonas aeruginosa (P. aeruginosa). The hybrid nanoparticles in eightfold‐lower concentration than the AgNPs inhibit 45% of the QS‐regulated virulence factors produced by the reporter Chromobacterium violaceum bacterial strain and reduce by 100% the P. aeruginosa biofilm formation. Moreover, the sequential deposition of antibacterial/antibiofilm active and biocompatible biopolymers onto the AgNPs allows the engineering of safe nanomaterials that do not affect the viability of human cells.     

Bacteria-Responsive Multidrug Delivery Nanosystem for Combating Long-Term Biofilm-Associated Infections

Microbial biofilm formation on implantable devices causes chronic infections that cannot be treated with existing antimicrobials. Quorum sensing inhibitors (QSIs) have recently emerged as novel antimicrobials for the prevention of biofilm formation. But blocking QS alone is insufficient to inhibit biofilm-associated chronic infections. Herein, chitosan hollow nanospheres are capped by bacteria-responsive β-casein to form a synergistic antifouling nanosystem consisting of a QSI and bactericide. β-casein is degraded by protease in a bacteria-colonized microenvironment in situ thus, QSI and bactericide are released sequentially. The release of QSI sensitises bacteria effectively through reduction of surface hydrophobicity, eDNA content, and lipopolysaccharide production in biofilms, amplifying the chemotherapeutic action of the bactericide. Compared to the uncoated surface, the coated surface inhibits biofilm formation and removes preformed biofilms of Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus by 1.8 logs and 1.9 logs of biomass inhibition, respectively. The coated catheters are found to stay clean for 30 days under artificial urine flow, while the uncoated catheters are clogged by bacterial biofilms within 5 days. Finally, the long term antifouling activity in vivo is confirmed. Overall, the nanosystem is devoted to making urinary catheters resistant to bacterial biofilm formation for the long term.     

Synergistic Antimicrobial and Antibiofilm Nanoparticles Assembled from Naturally Occurring Building Blocks

Bacterial infections represent one of the serious human healthcare threats, and ≈80% of bacterial infections are related to biofilm. So far, there are extensive investigations on the development of robust biomaterials toward the elimination of biofilms and synergistic antibacterial applications. Despite the progress made, concerns have always been raised regarding the sophisticated synthesis and pre-modification of hybrid materials, complicated purification and high-cost work. In this study, a series of robust and integrative nanoparticles (NPs) assembled from two types of natural building blocks (natural polyphenols and tobramycin antibiotics) is successfully fabricated via a one-pot integration approach, which can efficiently destruct the biofilm structure and kill bacteria via enhanced antibiotic infiltration. Notably, natural polyphenols and tobramycin can release from the formed NPs in an on-demand manner in the bacterial-induced environment. The former ones can inhibit quorum sensing within bacteria through competitive combination with autoinducer-2 (AI-2) to remove the existing biofilm, and the latter antibiotics exert high antibacterial activity both in vitro and in vivo. This study provides new inspirations toward robust and synergistic antimicrobial and antibiofilm nanomaterials via the facile integration of naturally occurring molecules.     

Biofilm-Sensitive Photodynamic Nanoparticles for Enhanced Penetration and Antibacterial Efficiency

Efficient antimicrobials are urgently needed for the treatment of bacterial biofilms due to their resistance to traditional drugs. Photodynamic therapy (PDT) is a new strategy that has been used to combat bacteria and biofilms. Cationic photosensitizers, particularly cationic photodynamic nanoagents, are usually chosen to enhance photodynamic antimicrobial activity. However, positively charged nanoparticles (NPs) are beneficial to cellular internalization, which causes increased cell cytotoxicity. Herein, a pH-sensitive photodynamic nanosystem is designed. Rose Bengal (RB) polydopamine (PDA) NPs are decorated in a layer-by-layer fashion with polymyxin B (PMB) and gluconic acid (GA) to generate functionally adaptive NPs (RB@PMB@GA NPs). RB@PMB@GA NPs remain negative at physiological pH and exhibit good biocompatibility. When RB@PMB@GA NPs are exposed to an acidic infectious environment, the surface charge of the NPs is, in turn, positively charged as a result of pH-sensitive electrostatic interactions. This surface charge conversion allows the RB@PMB@GA to effectively bind to the surfaces of bacteria and enhance photoinactivation efficiency against gram-negative bacteria. Most importantly, RB@PMB@GA NPs exhibit good biofilm penetration and eradication under acidic conditions. Furthermore, RB@PMB@GA NPs efficiently eliminate biofilm infections in vivo. This study provides a promising strategy for safely treating biofilm-associated infections in vivo.     

细菌外排泵抑制剂对光动力疗法防龋效果的影响

目的:探讨细菌外排泵抑制剂(microbial efflux pump Inhibitor,EPI)———维拉帕米对以甲苯胺蓝O(toluidine blue O,TBO)为光敏剂的光动力疗法(photodynamic therapy,PDT)抑制牙菌斑生物膜内主要致龋菌作用的影响。方法:以变形链球菌、血链球菌、嗜酸性乳杆菌和粘性放线菌为实验菌株,建立牙菌斑生物膜模型。以维拉帕米作为细菌外排泵抑制剂,根据在PDT过程中加入维拉帕米和光敏剂的先后顺序,实验分为5组。A组:生理盐水处理组。B组:单纯PDT处理组。C组:同时加入光敏剂和维拉帕米PDT处理组。D组:先加入维拉帕米后加入光敏剂PDT处理组。E组:先加入光敏剂后加入维拉帕米PDT处理组。平板菌落计数观察牙菌斑生物膜活性,并运用激光共聚焦显微镜(Confocal laser scanning microscopy,CLSM)对处理后的牙菌斑生物膜进行断层扫描、分析。结果:与生理盐水处理组相比,单纯PDT处理组牙菌斑内致龋菌存活的数量(CFU/mL)明显减少(P<0.05),其抑菌率为81.02%;与单纯PDT处理组相比,加入维拉帕米的PDT处理组内牙菌斑内致龋菌存活数量有下降趋势。其中先加入维拉帕米后加入光敏剂PDT处理组牙菌斑内致龋菌存活数量显著性下降(P<0.05),抑菌率高达93.60%;激光共聚焦显微镜观察发现菌斑生物膜发生明显的变化。结论:实验表明光动力疗法有明显的防龋效果,且细菌外排泵抑制剂对PDT防龋效果有促进作用。     

Antimicrobial Hybrid Amphiphile via Dynamic Covalent Bonds Enables Bacterial Biofilm Dispersal and Bacteria Eradication

To tackle the problems caused by bacterial biofilms, herein, this study reports an antimicrobial hybrid amphiphile (aHA) via dynamic covalent bonds for eradicating staphylococcal biofilms. aHA is synthesized via iminoboronate ester formation between DETA NONOate (nitric oxide donor), 3 4-dihydroxybenaldehyde, and phenylboronic acid-modified ciprofloxacin (Cip). aHA can self-assemble in aqueous solution with an ultra-small critical aggregation concentration of 3.80 × 10^–5 mm and high drug loading content of 73.8%. The iminoboronate ester is sensitive to the acidic and oxidative biofilm microenvironment, liberating nitric oxide and Cip that can synergistically eradicate bacterial biofilms. To this end, aHA assemblies efficiently eradicate staphylococcal infections and ameliorate inflammation in the murine peritoneal and subcutaneous infection models without any notable side effects on normal tissues. Collectively, the aHA assemblies may provide a facile and efficient alternative to the current development of anti-biofilm therapies.     

Functional Materials to Overcome Bacterial Barriers and Models to Advance Their Development

With the emerging problem of antimicrobial resistance, the world is facing a slow but dangerous pandemic. While the discovery of novel antibiotics is reaching a nearly exhaustive end, new concepts for anti-infective drugs are emerging. So-called pathoblockers aim to de-weaponize bacteria rather than just killing them. As the target of these molecules is typically located intracellularly, however, hitherto almost unnoticed biological barriers are emerging such as the biofilm matrix, the bacterial cell envelope, efflux pumps, and eventual bacterial metabolism. This leads to a new paradigm that is to maximize bacterial bioavailability. To overcome the bacterial barriers, especially when further optimization of the active molecules is not possible, functional materials are needed to engineer innovative delivery systems. Those may not only enable novel anti-infective molecules to reach their targets, but will also improve the bacterial bioavailability of existing anti-infectives. Additionally, there is a need for better infection models that allow studying drug effects on both the bacteria and the host in a relevant manner as needed for rational anti-infective drug development.     

Modulation of Intracellular Oxygen Pressure by Dual‐Drug Nanoparticles to Enhance Photodynamic Therapy

Oxygen plays an essential role in the photodynamic therapy (PDT) of cancer. However, hypoxia inside tumors severely attenuates the therapeutic effect of PDT. To address this issue, a novel strategy is reported for cutting off the oxygen consumption pathway by using sub‐50 nm dual‐drug nanoparticles (NPs) to attenuate the hypoxia‐induced resistance to PDT and to enhance PDT efficiency. Specifically, dual‐drug NPs that encapsulate photosensitizer (PS) verteporfin (VER) and oxygen‐regulator atovaquone (ATO) with sub‐50 nm diameters can penetrate deep into the interior regions of tumors and effectively deliver dual‐drug into tumor tissues. Then, ATO released from NPs efficiently reduce in advance cellular oxygen consumption by inhibition of mitochondria respiratory chain and further heighten VER to generate greater amounts of ¹O₂ in hypoxic tumor. As a result, accompanied with the upregulated oxygen content in tumor cells and laser irradiation, the dual‐drug NPs exhibit powerful and overall antitumor PDT effects both in vitro and in vivo, and even tumor elimination. This study presents a potential appealing clinical strategy in photodynamic eradication of tumors.     

Photo-Stimuli Smart Supramolecular Self-Assembly of Azobenzene/β-Cyclodextrin Inclusion Complex for Controlling Plant Bacterial Diseases

Controllable and on-demand delivery of supramolecular systems have received considerable attention in modern agricultural management, especially for managing intractable plant diseases. Here, an intelligent photoresponsive pesticide delivery system is reported based on β-cyclodextrin (β-CD) and azobenzene, which overcomes the resistance of phytopathogens caused by the irrational use of conventional pesticides. Antibacterial bioassays illustrated that designed azobenzene derivative 3a possesses the most efficient bioactivity with EC₅₀ values of 0.52–25.31 µg mL⁻¹ toward three typical phytopathogens. Moreover, the assembly of the supramolecular binary complex 3a @β-CD is successfully elucidated and displays exceptional inhibitory activity on biofilm formation. Of note, this supramolecular binary complex significantly improves the water solubility, foliar surface wettability, and shows marked light-responsive properties. In vivo anti-Xoo assays reveal that 3a @β-CD has excellent control efficiency (protective activity: 51.22%, curative activity: 48.37%) against rice bacterial blight pathogens, and their control efficiency can be elevated to values of 55.84% (protective activity) and 52.05% (curative activity) by UV–vis exposure. In addition, the 3a @β-CD are non-toxic toward various non-target organisms. This study therefore offers new insights into the potential of host-guest complexes as a feasible pesticide discovery strategy characterized by a safe, biocompatible, light-responsive release, and antibiofilm properties for overcoming intractable plant bacterial diseases.     

pH‐Responsive Polymer–Drug Conjugate: An Effective Strategy to Combat the Antimicrobial Resistance

An urgent need for developing new antimicrobial approaches has emerged due to the imminent threat of antimicrobial‐resistant (AMR) pathogens. Bacterial infection can induce a unique microenvironment with low pH, which can be employed to trigger drug release and activation. Here, a pH‐responsive polymer–drug conjugate (PDC) capable of combating severe infectious diseases and overcoming AMR is reported. The PDC is made of a unique biodegradable and biocompatible cationic polymer Hex‐Cys‐DET and streptomycin, a model antibiotic. The two components show strong antimicrobial synergy since the polymer can induce pores on the bacterial wall/membrane, thus significantly enhancing the transport of antibiotics into the bacteria and bypassing the efflux pump. The PDC is neutralized for enhanced biocompatibility under physiological conditions but becomes positively charged while releasing the antibiotic in infected tissues due to the low pH. Additionally, the polymer contains disulfide bonds in its main chain, which makes it biodegradable in mammalian cells and thus reducing the cytotoxicity. The PDC can effectively penetrate bacterial biofilms and be taken up by mammalian cells, thereby minimizing biofilm‐induced AMR and intracellular infections. The PDC exhibits remarkable antimicrobial activity in three in vivo infection models, demonstrating its broad‐spectrum antimicrobial capability and great potency in eliminating AMR infections.     

Smart Trap-Capture-Kill Antibacterial System for Infected Microenvironment Improvement and Vascularized Bone Regeneration via Magnetic Thermotherapy

Infected bone defect has gradually become a disastrous complication in orthopedic surgery because of the bacterial biofilm formation both on the surface of the implants and surrounding tissues, which will cause antibiotic resistance and weak postoperative osseointegration. Herein, drug-loaded hollow mesoporous ferrite nanoparticles coated by gelatin (GM/HMFNs) with pomegranate structure are prepared and compounded into calcium magnesium phosphate cement (MCPC) as a Trap-Capture-Kill system to kill bacteria and inhibit biofilm formation efficiently. Under the action of alternating magnetic field (AMF), MCPC/GM/HMFNs/Drug composites exhibit acute magnetic hyperthermal capacity and recruit the free bacteria. Then, the permeability of bacterial cell membrane is increased via reactive oxygen species (ROS) damage of nano-MgO and HMFNs, providing channels through which vancomycin (Van) and ciprofloxacin (CPFX) encapsulated in GM/HMFNs can penetrate. Subsequently, the bacteria are efficiently killed under the synergetic cooperation of magnetothermal effect, ROS damage, and adsorption damage of nano-MgO, and the bioactive ions and drugs. The antibacterial system also presents outstanding pro-osteogenesis and pro-angiogenic capacity in vitro. And it promotes the vascularized bone regeneration of infective femoral defect in SD rats in vivo, providing promising potential for the treatment of infected bone defects through magnetothermal therapy.     

Electroaddressing Functionalized Polysaccharides as Model Biofilms for Interrogating Cell Signaling

Bacteria often reside at surfaces as complex biofilms in which an exopolysaccharide matrix entraps the population while allowing access to its chemical environment. There is a growing awareness that the biofilm structure and activity are integral to a wide array of properties important to health (the microbiome), disease (drug resistance) and technology (fouling). Despite the importance of bacterial biofilms, few experimental platforms and systems are available to assemble complex populations and monitor their activities. Here, a functionalized alginate composite material for creating in vitro model biofilms suitable for cell‐cell signaling studies by entrapping bacterial cells in situ is reported. Biofilm assembly is achieved using device‐imposed electrical signals to electrodeposit the stimuli‐responsive polysaccharide alginate. This electrodeposition mechanism is versatile in that it allows control of the bacterial population density and distribution. For instance, it is demonstrated that a mixed population can be homogeneously distributed throughout the biofilm or can be assembled as spatially segregated populations within a stratified biofilm. The “electroaddressable” biofilms are visualized using both a planar 2D chip with patterned electrodes and a microfluidic bioMEMS device with sidewall electrodes. Specifically, it is observed that bacteria entrapped within the model biofilm recognize and respond to chemical stimuli imposed from the fluidic environment. Finally, reporter cells are used to demonstrate that bacteria entrapped within this model biofilm engage in intercellular quorum sensing. This work demonstrates the functionality of the stimuli‐responsive polysaccharide by biofabricating pseudo‐3D cell‐gel biocomposites, mimicking the formation of biofilms, for interrogating phenotypes of E. coli bacterial populations. In addition to controlling assembly, the microfluidic device allows the biofilm to be monitored through the fluorescence methods commonly used in biological research. This platform technology should be able to be exploited for monitoring biofilm development, as well as for extending the understanding of the interactions between various bacterial species arranged in controlled patterns.     

Mitochondria-Targeted Photodynamic and Mild-Temperature Photothermal Therapy for Realizing Enhanced Immunogenic Cancer Cell Death via Mitochondrial Stress

Induction of immunogenic cell death (ICD) represents a robust therapeutic strategy for cancer treatment. However, only a few ICD inducers are currently available and many of them take effect based on traditional endoplasmic reticulum (ER) stress rather than mitochondrial stress. Besides, mitochondrion is closely related to ER and drug delivery via mitochondrial targeting usually shows a higher efficiency and cytotoxicity than that via ER targeting, which inspires to explore the ICD effect of cancer cells through mitochondrial stress. Herein, a mito-missile that can realize not only mitochondria-targeted photodynamic therapy (PDT)/mild-temperature photothermal therapy (MTPTT) but also ICD-induced cancer immunotherapy is constructed. The mito-missile (termed DIH) is prepared by coating dc-IR825 (a mitochondrion-targeting cyanine dye)-loaded polyamidoamine dendrimer with hyaluronic acid. dc-IR825 can precisely target mitochondria and produce reactive oxygen species (ROS) and mild heat upon near-infrared (NIR) light irradiation, inducing mitochondrial damage and mitochondrial stress-caused enhanced ICD. By combining PDT, MTPTT, and ICD-induced immunotherapy, the DIH mito-missile can efficiently inhibit tumor growth and even eradicate tumors. This study develops a dendrimer-based nanoplatform for realizing mitochondrion-acting PDT/MTPTT as well as mitochondrial stress-induced potentiated ICD, which may provide a guideline for designing effective ICD inducers in the future.     

Porphyrin MOF Dots–Based,Function‐Adaptive Nanoplatform for Enhanced Penetration and Photodynamic Eradication of Bacterial Biofilms

Recently, antimicrobial photodynamic therapy (aPDT) has been considered as an attractive treatment option for biofilms ablation. However, even very efficient photosensitizers (PSs) still need high light doses and PS concentrations to eliminate biofilms due to the limited penetration and diffusion of PSs in biofilms. Moreover, the hypoxic microenvironment and rapid depletion of oxygen during PDT severely limit their therapeutic effects. Herein, for the first time, a porphyrin‐based metal organic framework (pMOF) dots–based nanoplatform with effective biofilm penetration, self‐oxygen generation, and enhanced photodynamic efficiency is synthesized for bacterial biofilms eradication. The function‐adaptive nanoplatform is composed of pMOF dots encapsulated by human serum albumin–coated manganese dioxide (MnO₂). The pH/H₂O₂‐responsive decomposition of MnO₂ in biofilms triggers the release of ultra‐small and positively charged pMOF dots and simultaneously generates O₂ in situ to alleviate hypoxia for biofilms. The released pMOF dots with high reactive oxygen species yield can effectively penetrate into biofilms, strongly bind with bacterial cell surface, and ablate bacterial biofilms. Importantly, such a nanoplatform can realize great therapeutic outcomes for treatment of Staphylococcus aureus–infected subcutaneous abscesses in vivo without damage to healthy tissues, which offers a promising strategy for efficient biofilms eradication.     

An Iridium (III) Complex Bearing a Donor–Acceptor–Donor Type Ligand for NIR-Triggered Dual Phototherapy

Iridium(III) complexes are an important group of photosensitizers for photodynamic therapy (PDT). This work constructs a donor–acceptor–donor structure-based iridium(III) complex (IrDAD) with high reactive oxygen species (ROS) generation efficiency, negligible dark toxicity, and synergistic PDT and photothermal therapy (PTT) effect under near-infrared (NIR) stimulation. This complex self-assembles into metallosupramolecular aggregates with a unique aggregation-induced PDT behavior. Compared with conventional iridium(III) photosensitizers, IrDAD not only achieves NIR light deep tissue penetration but also shows highly efficient ROS and heat generation with ROS quantum yield of 14.6% and photothermal conversion efficiency of 27.5%. After conjugation with polyethylene glycol (PEG), IrDAD is formulated to a nanoparticulate system (IrDAD-NPs) with good solubility. In cancer phototherapy, IrDAD-NPs preferentially accumulate in tumor area and display a significant tumor inhibition in vivo, with 96% reduction in tumor volume, and even tumor elimination.     

Bacterial Outer Membrane-Coated Mesoporous Silica Nanoparticles for Targeted Delivery of Antibiotic Rifampicin against Gram-Negative Bacterial Infection In Vivo

The efficacy of conventional antibiotics therapeutics has declined rapidly due to the emerged antibiotic resistance. There is an urgent need to develop novel approaches to address the problem of antibiotic shortage, particularly for Gram-negative bacteria. Herein, a biomimetic nanodelivery system is proposed to enhance the bacterial targeting and uptake of rifampicin (Rif), a traditional antibiotic but not effective against Gram-negative bacteria. The biomimetic nanodelivery system (Rif@MSN@OMV) is composed of outer membrane vesicles (OMVs) isolated from E. coli as shell and rifampicin-loaded mesoporous silica nanoparticles (MSNs) as core. The OMVs greatly improve the uptake of MSNs in E. coli, but not in Gram-positive bacteria S. aureus, owing to the homotypic targeting function of the OMVs. The Rif@MSN@OMV exhibits enhanced antimicrobial activity against E. coli and completely eradicates bacteria at an equivalent rifampicin concentration (4 µg mL⁻¹) while free rifampicin shows weak bactericidal activity. Meanwhile, the Rif@MSN@OMV maintains good biocompatibility both in vitro and in vivo. More importantly, the Rif@MSN@OMV elevates survival rate of infected mice and reduces bacterial load in intraperitoneal fluid and organs. Overall, the OMVs-coated nanodelivery system provides a novel strategy to improve the antimicrobial efficacy of conventional antibiotic or repurpose drugs for treatment of Gram-negative bacterial infections.     

pH Switchable Nanoplatform for In Vivo Persistent Luminescence Imaging and Precise Photothermal Therapy of Bacterial Infection

Photothermal therapy (PTT) is one of the most promising approaches to combat multidrug‐resistant bacteria with less potential to induce resistance and systemic toxicity. However, uncontrollable distribution of photothermal agents leads to lethal temperatures for normal cells, and failure to offer timely and effective antibacterial stewardship. A pH switchable nanoplatform for persistent luminescence imaging‐guided precise PTT to selectively destroy only pathological cells while protecting nearby normal cells in bacterial infected microenvironment is shown. The PLNP@PANI‐GCS is fabricated by grafting polyaniline (PANI) and glycol chitosan (GCS) onto the surface of persistent luminescence nanoparticles (PLNPs). It takes advantage of the long persistent luminescence of PLNPs to realize autofluorescence‐free imaging, the pH‐dependent light–heat conversion property of PANI to get a stronger photothermal effect at pH 6.5 than pH 7.4, and the pH environment responsive surface charge transition of GCS. Consequently, PLNP@PANI‐GCS enables effective response to bacterial‐infected acid region and electrostatic bonding to bacteria in vivo, ensuring the spatial accuracy of near‐infrared light irradiation and specific heating directly to bacteria. In vivo imaging‐guided PTT to bacterial infection abscess shows effective treatment. PLNP@PANI‐GCS has great potential in treating multidrug‐resistant bacterial infection with low possibility of developing microbial drug resistance and little harm to normal cells.     

Eradication of Multidrug‐Resistant Staphylococcal Infections by Light‐Activatable Micellar Nanocarriers in a Murine Model

Bacterial infections are mostly due to bacteria in their biofilm mode‐of‐growth, making them recalcitrant to antibiotic penetration. In addition, the number of bacterial strains intrinsically resistant to available antibiotics is alarmingly growing. This study reports that micellar nanocarriers with a poly(ethylene glycol) shell fully penetrate staphylococcal biofilms due to their biological invisibility. However, when the shell is complemented with poly(β‐amino ester), these mixed‐shell micelles become positively charged in the low pH environment of a biofilm, allowing not only their penetration but also their accumulation in biofilms without being washed out, as do single‐shell micelles lacking the pH‐adaptive feature. Accordingly, bacterial killing of multidrug resistant staphylococcal biofilms exposed to protoporphyrin IX‐loaded mixed‐shell micelles and after light‐activation is superior compared with single‐shell micelles. Subcutaneous infections in mice, induced with vancomycin‐resistant, bioluminescent staphylococci can be eradicated by daily injection of photoactivatable protoporphyrin IX‐loaded, mixed‐shell micelles in the bloodstream and light‐activation at the infected site. Micelles, which are not degraded by bacterial enzymes in the biofilm, are degraded in the liver and spleen and cleared from the body through the kidneys. Thus, adaptive micellar nanocarriers loaded with light‐activatable antimicrobials constitute a much‐needed alternative to current antibiotic therapies.     

Multifunctional and Recyclable Photothermally Responsive Cryogels as Efficient Platforms for Wound Healing

A growth in the use of antibiotics and the related evolution of patients' drug resistance calls for an urgent response for the development of novel curing approaches without using synthetic antibiotics. Here, the fabrication of a low‐cost cryogel for wound dressing applications is demonstrated. The cryogel is composed of only naturally derived components, including chitosan/silk fibroin as the scaffold and tannic acid/ferric ion (TA/Fe³⁺) as the stimuli‐responsive agent for photothermal therapy. Based on the multiple weak hydrogen bonds and metal ligand coordination, the cryogel exhibits good flexibility and recoverability. Its highly porous structure renders the cryogel to be strongly hygroscopic to absorb blood for hemostasis. The cryogel exhibits excellent antibacterial activity to both Gram‐negative and positive bacteria, benefiting from the high photothermal transition activity of the TA/Fe³⁺ complex. Furthermore, the cryogel can efficiently promote cell proliferation in vitro. Significantly, animal experiments also reveal that the cryogel effectively eradicate microbes at the wound and accelerate the wound healing process. In summary, this novel biorenewable cryogel demonstrates excellent hygroscopic and hemostatic performance, photothermal antimicrobial activity, and accelerates skin regeneration, which has great application potential as a promising wound dressing material in the clinical use.