Mitochondria-Targeted Natural Antioxidant Nanosystem for Diabetic Vascular Calcification Therapy.

The development of nanotherapy targeting mitochondria to alleviate oxidative stress is a critical therapeutic strategy for vascular calcification (VC) in diabetes. In this study, we engineered mitochondria-targeted nanodrugs (T4O@TPP/PEG-PLGA) utilizing terpinen-4-ol (T4O) as a natural antioxidant and mitochondrial protector, PEG-PLGA as the nanocarrier, and triphenylphosphine (TPP) as the mitochondrial targeting ligand. In vitro assessments demonstrated enhanced cellular uptake of T4O@TPP/PEG-PLGA, with effective mitochondrial targeting. This nanodrug successfully reduced oxidative stress induced by high glucose levels in vascular smooth muscle cells. In vivo studies showed prolonged retention of the nanomaterials in the thoracic aorta for up to 24 h. Importantly, experiments in diabetic VC models underscored the potent antioxidant properties of T4O@TPP/PEG-PLGA, as evidenced by its ability to mitigate VC and restore mitochondrial morphology. These results suggest that these nanodrugs could be a promising strategy for managing diabetic VC.

Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer.

BACKGROUND: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility. RESULTS: Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages. CONCLUSION: Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.

Enhanced of antibacterial activity of antibiotic-functionalized silver nanocomposites with good biocompatibility.

Antimicrobial resistance to traditional antibiotics leads to a serious concern for medical care owing to ineffective antibiotic therapies. This study focused on the preparation of silver nanocomposites (AgNPs@Tob&PAGA) by modifying AgNPs with tobramycin (Tob) and carbohydrate polymer of poly(2-(acrylamido) glucopyranose) (PAGA). The enhanced antibacterial activities of nanocomposites against common pathogens of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were explored. The introduction of PAGA onto silver nanocomposites improved both citocompatibility and antibacterial activity. Compared with nude Tob, AgNPs@Tob&PAGA showed more fascinating antimicrobial effect against E. coli and S. aureus with about 20-fold increase in the antibacterial activity, simultaneously no detectable resistance was observed. Consequently, the silver nanocomposite as an antimicrobial agent presents promising prospects in the treatment of bacterial infections caused by antimicrobial resistant bacteria.

A W/O emulsion mediated film dispersion method for curcumin encapsulated pH-sensitive liposomes in the colon tumor treatment.

The CaCO3 encapsulated liposome with pH sensitivity is an efficient carrier for the delivery of chemotherapeutic drugs. Herein, we provided an innovative method that take advantage of a W/O emulsion to prepare CaCO3 encapsulated liposomes for the delivery of curcumin. The liposomes with both CaCO3 and curcumin encapsulated (LCC) showed high sensitivity to reduced pH (the environment of lysosomes). Due to the inherent pH sensitivity of CaCO3, LCC swelled and released the encapsulated curcumin rapidly in acidic medium. The lysosome escape capability and promoted accumulation of curcumin in the cytosol from LCC was verified with respect to that of curcumin loaded liposomes (CLIPO). Despite the similar cytotoxicity within curcumin preparations in vitro at high concentration, LCC exhibited optimal antitumor effect in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal cancer model, which was attributed to the long circulation time and efficient intracellular delivery of curcumin from LCC. It is suggested that the solubility and cytosolic delivery of curcumin are greatly improved by LCC, which accounts for the increased pharmacodynamic effect of curcumin. Thus, the CaCO3 encapsulated liposomes developed in this study is an ideal carrier for the hydrophobic drugs in potential clinical application.

Block versus Random Amphiphilic Glycopolymer Nanopaticles as Glucose-Responsive Vehicles.

To explore the effect of polymer structure on their self-assembled aggregates and their unique characteristics, this study was devoted to developing a series of amphiphilic block and random phenylboronic acid-based glycopolymers by RAFT polymerization. The amphiphilic glycopolymers were successfully self-assembled into spherically shaped nanoparticles with narrow size distribution in aqueous solution. For block and random copolymers with similar monomer compositions, block copolymer nanoparticles exhibited a more regular transmittance change with the increasing glucose level, while a more evident variation of size and quicker decreasing tendency in I/I0 behavior in different glucose media were observed for random copolymer nanoparticles. Cell viability of all the polymer nanoparticles investigated by MTT assay was higher than 80%, indicating that both block and random copolymers had good cytocompatibility. Insulin could be encapsulated into both nanoparticles, and insulin release rate for random glycopolymer was slightly quicker than that for the block ones. We speculate that different chain conformations between block and random glycopolymers play an important role in self-assembled nanoaggregates and underlying glucose-sensitive behavior.

An Acid-Triggered Degradable and Fluorescent Nanoscale Drug Delivery System with Enhanced Cytotoxicity to Cancer Cells.

To reduce side-effects of anticancer drugs, development of nanocarriers with precise biological functions is a critical requirement. In this study, the multifunctional nanoparticles combining imaging and therapy for tumor-targeted delivery of hydrophobic anticancer drugs were prepared via self-assembly of amphiphilic copolymers obtained using RAFT polymerization, specifically, acid-labile ortho ester and galactose. First, boron-dipyrromethene dye-conjugated chain transfer agent provides fluorescent imaging capability for diagnostic application. Second, nanoparticles were stable under physiological conditions but degraded in acidic tumor microenvironment, leading to enhanced anticancer efficacy. Third, the application of biocompatible glycopolymers efficiently increased the target-to-background ratio through carbohydrate-protein interactions. Data from cell viability, cellular internalization, flow cytometry, biodistribution and anticancer efficacy tests showed that the drug-loaded nanoparticles were capable of inhibiting cancer cell proliferation with significantly enhanced capacity. Our newly developed multifunctional nanoparticles may thus facilitate the development of effective drug delivery systems for application in diagnosis and therapy of cancer.

Phenylboronate-diol crosslinked glycopolymeric nanocarriers for insulin delivery at physiological pH.

Research into polymers with glucose-sensitivity in physiological conditions has expanded recently due to their therapeutic potential in diabetes. Herein, to explore the glucose-responsive properties of a new polymer under physiological conditions, we synthesized an amphiphilic block glycopolymer based on phenylboronic acid and a carbohydrate, which was named poly(d-gluconamidoethyl methacrylate-block-3-acrylamidophenylboronic acid) (p(AAPBA-b-GAMA)). Based on the cross-linking between the diol groups of the carbohydrates and phenylboronic acid, the glycopolymers self-assembled to form nanoparticles (NPs). The glucose-sensitivity was revealed by the swelling behavior of the NPs at different glucose concentrations and was found to be dependent on the glucose level. The morphology of the NPs revealed by transmission electron microscopy showed that the NPs were spherical in shape with good dispersity. The cell viability of the NPs investigated by MTT assay was more than 90%, indicating that the glycopolymers had good cytocompatibility. Insulin could be loaded onto the glycopolymer NPs with high efficiency (up to 10%), and insulin release increased with enhancement of the glucose level in the medium. Such a glucose-responsive glycopolymer is an excellent candidate that holds great potential in the treatment of diabetes.

Glucose-sensitive polyelectrolyte nanocapsules based on layer-by-layer technique for protein drug delivery.

The glucose-responsive nanocapsules [CS-NAC/p(GAMA-r-AAPBA)] were readily fabricated with modified chitosan (CS-NAC) and random glycopolymer poly(D-gluconamidoethyl methacrylate-r-3-acrylamidophenylboronic acid) p(GAMA-r-AAPBA) as the alternant multilayered polyelectrolyte hybrid shell via layer-by-layer self-assembly after etching the amino functionalized SiO2 spheres by NH4F/HF. The spherical and hollow structure of nanocapsules was confirmed by TEM analysis and there was no clear collapse found after removal of the sacrificial cores. The reversible zeta potential changes of the nanocapsule materials evaluated the reversible glucose sensitivity. Besides, this system demonstrated a good capacity for encapsulation and loading insulin entrapped in nanocapsules as model protein drug. A good biocompatibility of the material was confirmed by the cell viability. In vitro release of insulin experiments revealed that no obvious release was found in acidic condition and the release could be normally conducted at physiological pH. These results implied that it was feasible for nanocapsules to be used in controlled release drug delivery system.

Insights into the molecular characteristics of embryonic cranial neural crest cells and their derived mesenchymal cell pools.

Neural crest cells (NCCs) are central to vertebrate embryonic development, giving rise to diverse cell types with unique migratory and differentiation capacities. This study examines the molecular characteristics of cranial neural crest cell (CNCC)-derived mesenchymal cells, specifically those from teeth which in deer show continuous but limited growth, and antlers, which exhibit remarkable regenerative capabilities. Here, through single-cell RNA sequencing analysis, we uncover shared gene expression profiles between adult antlerogenic and dental mesenchymal cells, indicating common developmental pathways. We identify a striking resemblance in transcriptomic features between antlerogenic progenitor cells and dental pulp mesenchymal cells. Comparative analysis of CNCC-derived and non-CNCC-derived mesenchymal cell pools across species reveals core signature genes associated with CNCCs and their derivatives, delineating essential connections between CNCCs and CNCC-derived adult mesenchymal pools. Furthermore, whole-genome DNA methylation analysis unveils hypomethylation of CNCC derivate signature genes in regenerative antlerogenic periosteum, implying a role in maintaining multipotency. These findings offer crucial insights into the developmental biology and regenerative potential of CNCC-derived mesenchymal cells, laying a foundation for innovative therapeutic strategies in tissue regeneration.

Conditioned media of deer antler stem cells accelerate regeneration of alveolar bone defects in rats.

The destruction of periodontal alveolar bone (AB) caused by periodontitis is regarded as one of the major reasons for tooth loss. The inhibition of bone resorption and regeneration of lost AB are the desirable outcomes in clinical practice but remain in challenge. The use of mesenchymal stem cells (MSCs) is one current approach for achieving true restoration of AB defects (ABD). Antler stem cells (AnSC) are capable of renewing a huge mammalian bony appendage, the deer antler, suggesting an unparalleled potential for bone regeneration. Herein, we investigated the effectiveness of deer AnSCs conditioned medium (CM, AnSC-CM) for repair of surgically-created ABD using a rat model and sought to define the underlying mechanisms. The results showed that AnSC-CM effectively induced regeneration of AB tissue; the outcome was significantly better than human bone marrow mesenchymal stem cell conditioned medium (hBMSC-CM). AnSC-CM treatment upregulated osteogenic factors and downregulated osteoclastic differentiation factors; stimulated proliferation, migration and differentiation of resident MSCs toward osteogenic lineage cells; modulated macrophage polarization toward the M2 phenotype and suppressed osteoclastogenesis. That AnSC-CM resulted in better outcomes than hBMSC-CM in treating ABD was attributed to the cell compatibility as both AnSCs and AB tissue are neural crest-derived. In conclusion, the effects of AnSC-CM on AB tissue regeneration were achieved through both promotion of osteogenesis and inhibition of osteoclastogenesis. We believe that AnSC-CM is a candidate for effective treatment of ABD in dental clinical practice but will require investment in further development.

Deer Antler Reserve Mesenchyme Cell-Conditioned Medium Reduces the Destruction of Periodontitis in Mice.

Reserve mesenchyme cells (RMCs) are a type of antler stem cells (ASCs) that contribute to the rapid growth of deer antlers, the only known mammalian organ that can fully regenerate annually. Based on the prior evidence, ASC-conditioned medium could improve regenerative cutaneous healing in rats. The purpose of the study was to evaluate the therapeutic effects of RMC-conditioned medium (RMC-CM) on reducing the destruction in the mice periodontitis (PD) model and the underlying mechanisms. The lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used in vitro to verify the effects of RMC-CM. The results revealed that RMC-CM could significantly reduce bone resorption and osteoclast activation, upregulate anti-inflammatory macrophages (M2) related interleukin (IL)-10 and CD206, and downregulate pro-inflammatory macrophages (M1) related tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase in vivo. In vitro, RMC-CM could significantly promote LPS-stimulated RAW264.7 cells migration, reduce osteoclast differentiation, downregulate the expression of TNF-α, IL-6, and IL-1ß, and upregulate the expression of IL-10 and arginase 1. According to the results, we concluded that RMC-CM could significantly reduce alveolar bone resorption and inhibit inflammation in gingival tissue by decreasing the activation of osteoclasts and inducing macrophage polarization toward the M2 phenotype. This study may serve as the experimental foundation for RMC-CM in the treatment of PD.

Systemic Delivery of mPEG-Masked Trispecific T-Cell Nanoengagers in Synergy with STING Agonists Overcomes Immunotherapy Resistance in TNBC and Generates a Vaccination Effect.

T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The "immunologically cold" solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed. PmTriTNE@CDA shows tumor-specific accumulation and is preferentially unmasked in response to a weakly acidic TME to prevent on-target off-tumor toxicity. The unmasked CD44×PD-L1/CD3 trispecific T-cell nanoengager (TriTNE) targets dual tumor-associated antigens (TAAs) to redirect CD8+ T cells for heterogeneous TNBC lysis while achieving PD-L1 blockade. PmTriTNE synergized with CDA to transform the cold tumor into a hot tumor, eradicate the large established TNBC tumor, and induce protective immune memory in a 4T1 orthotopic tumor model without causing obvious toxicity. PmTriTNE@CDA shows potent efficacy in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. This study serves as a proof-of-concept demonstration of a nanobased TCEs strategy to expand therapeutic combinations that previously could not be achieved due to systemic toxicity with the aim of overcoming TNBC heterogeneity and immunotherapy resistance.

Antibacterial Photodynamic Gold Nanoparticles for Skin Infection.

Damage or injury to the skin creates wounds that are vulnerable to bacterial infection, which in turn retards the process of skin regeneration and wound healing. In patients with severe burns and those with chronic diseases, such as diabetes, skin infection by multidrug-resistant bacteria can be lethal. Therefore, a broad-spectrum therapy to effectively eradicate bacterial infection through a mechanism different from that of antibiotics is much sought after. We successfully synthesized antibacterial photodynamic gold nanoparticles (AP-AuNPs), which are self-assembled nanocomposites of an antibacterial photodynamic peptide and poly(ethylene glycol) (PEG)-stabilized AuNPs. The AP-AuNPs exhibited aqueous and light stability, a satisfactory generation of reactive oxygen species (ROS), and a remarkable antibacterial effect toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli upon light irradiation. Moreover, the synthesized nanocomposites significantly inhibited bacterial growth and biofilm formation in vitro. Photodynamic antibacterial treatment accelerated the wound-healing rate in S. aureus infections, mimicking staphylococcal skin infections. Using a combination of the bactericidal effect of a peptide, the photodynamic effect of a photosensitizer, and the multivalency clustering on AuNPs for maximal antibacterial effect under light irradiation, we synthesized AP-AuNPs as a wound-dressing nanomaterial in skin infections to promote wound healing. Our findings indicate a promising strategy in the management of bacterial infections resulting from damaged skin tissue, an aspect that has not been fully explored by our peers.

Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity.

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain BbDrE@BA/CPX, BrDbE@BA/CPX, and BrDrE@BA/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%-95% release in pH 5.5 over 24 h and 15%-30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2-8 fold reduction for CPX) or single drug-loaded nanocomposites (4-8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.

[Relationships among the periodontal biotype characteristics in the maxillary anterior].

OBJECTIVE: To explore the correlation among gingival thickness (GT), underlying alveolar bone thickness (BT), and other periodontal biotype characteristics in the maxillary anterior. METHODS: A total of 40 young volunteers with healthy periodontal were involved in this research. The periodontal probe was previously used to divide the gingiva from thick to thin. Two records were measured by cone beam CT (CBCT) GT, which was measured at the cement-enamel junction level; and BT, which was measured at 3 locations: 1, 3, 5 mm below the alveolar crest. Oral and gypsum measurements were used to analyze the associations of the crown width/crown length ratio (CW/CL), the keratinized mucosa width (KM), and the free gingival margin curvature. RESULTS: Significant difference in the GT was observed between the thick and thin biotypes, which were divided by periodontal probe (P<0.01). Difference was observed in each periodontal biotype characteristic between the thick (GT≥1 mm) and thin biotypes (GT<1 mm) (P<0.05). BT was positively associated with GT (r=0.293, P=0.001), CW/CL (r=0.273, P=0.003), KM (r=0.291, P=0.001), and free gingival margin curvature (r=0.290, P=0.001). CONCLUSIONS: The transparency of the probing in the sulcus could analyze the GT qualitatively. The thick and thin biotypes have different periodontal biotype characteristics. Compared with individuals with thick biotype, those with thin biotype are susceptible to risk dental aesthetic.

Assessment of biomass demineralization on gasification: From experimental investigation, mechanism to potential application.

Considering the advantages (e.g. agglomeration mitigation) and disadvantages (e.g. inorganic species catalysis removal) of biomass demineralization, it is valuable to investigate its effects on gasification performance, thus assessing its necessity prior to performing gasification. To accomplish this, corn straw (CS) was demineralized to different degrees with H2O and HCl, respectively. H2O and HCl demineralization behaved different abilities to inorganic species removal. Cellulose and hemicelluloses content decreased, while lignin content increased, especially with HCl demineralization. The experiments were investigated by using a bench-scale downdraft fixed-bed gasifier at 600-800 °C and were further analyzed via thermogravimetric coupled with Fourier transform infrared spectrometry. Demineralization demonstrated a positive effect on gasification at lower temperatures (600-700 °C) for a dominant effect of lignin content and an insignificant effect of inorganic species removal. However, the catalysis of inorganic species increased as the temperature increased, resulting in the highest H2 (11.30 vol%) and CO (16.02 vol%) production of raw CS compared to demineralized CS at 800 °C. Inorganic species had a dual positive effect on CO generation, promoting both CO2 and char generation leading to a higher CO yield following Boundouard reaction, and increasing the formation of active intermediates thus producing more CO. These effects enhanced when the gasification temperature increased. Additionally, inorganic species catalyzed the aromatic rings rearrangement to generate more H2O, thus driving the endothermic Primary water-gas to produce H2. This was also positively correlated with gasification temperature. Therefore, raw CS demonstrated higher H2 and CO production than demineralized CS at a higher gasification temperature. Moreover, the promotion effect of inorganic species on thermal devolatilization of methoxyl groups and Methanation reaction led to the higher CH4 production of raw CS. This research clarifies the effects of biomass demineralization on its gasification and suggests the potential application.

Co-delivery of doxorubicin and epacadostat via heparin coated pH-sensitive liposomes to suppress the lung metastasis of melanoma.

High metastasis is responsible for the failure in the treatment of melanoma. Chemoimmunotherapy has shown conspicuous inhibition effects not only on the growth of tumor in situ, but also on the metastasis to distant organs. Given that the indoleamine-2,3 dioxygenase (IDO) overexpressed in the microenvironment of tumor leads to the immune escape, the combination of chemotherapeutic drug and IDO inhibitor might be a promising chemoimmunotherapy. Besides, the hematogenous metastasis mediated by platelets was supposed to be blocked by the heparin (HP). Therefore, a drug delivery system with all these elements involved might be a potential treatment for melanoma. Here, we developed a pH-sensitive liposomal dual-delivery system for doxorubicin (DOX) and epacadostat (EPA) with HP coated (HP/LDE). It was confirmed to enhance cytotoxicity and apoptosis, reverse the platelets-activated epithelial mesenchymal transformation (EMT) and prevent the invasion and migration in vitro. After systemic administration, HP/LDE provided the optimum anti-metastasis effect on the melanoma. The results of evaluation on DC maturation, CD8+ cytotoxic T lymphocytes (CTLs) activation and T cell mediated cytotoxicity were consistent in vitro and in vivo. Taken together, our study established a functional liposomal dual-delivery system with ideal anti-metastasis efficacy on melanoma.

Oral biofilm elimination by combining iron-based nanozymes and hydrogen peroxide-producing bacteria.

Dental caries is a global risk in terms of oral health in many schoolchildren and in a vast majority of adults. The primary factor for caries formation is the attachment of bacteria on the tooth surface to form an oral biofilm which generates acids to demineralize calcium and eventually cause tooth decay. Oral biofilm elimination is still a challenge because bacteria are embedded inside with the biofilm matrix protecting them, preventing the penetration of antibiotics or bactericides. Promising strategies for disrupting oral biofilms have been developed, including the use of natural enzymes to degrade the biofilm matrix and hydrogen peroxide to kill bacteria. Here we demonstrate a strategy that combines nanozymes with peroxidase-like activity and bacteria generating biogenic hydrogen peroxide to eliminate oral biofilms for caries treatment. By using a saliva-coated hydroxyapatite disc and sectioned human tooth to mimic the real oral environment, we analyze the influence of iron oxide nanozymes or iron sulfide nanozymes on a Streptococcus mutans biofilm in the presence of Streptococcus gordonii which can generate hydrogen peroxide. Bacterial viability assays and biofilm morphology characterization show that the combination of nanozymes and bacteria remarkably reduces the bacteria number (5 lg reduction) and biofilm matrix (85% reduction). Therefore, the combination of iron-based nanozymes and hydrogen peroxide-generating bacteria may provide a new strategy for oral biofilm elimination in dental caries treatment.

Polyethyleneimine and quaternized ammonium polyethyleneimine: the versatile materials for combating bacteria and biofilms.

Bacterial infection has become a serious clinical concern due to the emergence of drug-resistance and biofilm formation. Therefore, it is in great demand to develop efficient antimicrobial agents to treat bacterial infection without using antibiotics. Herein, we successfully prepared four quaternized ammonium PEI (QPEI: PEI1200-C2, PEI1200-C4, PEI1200-C6 and PEI1200-C8) using the commercial available PEI1200. Both PEI and four QPEI presented broad-spectrum antimicrobial activity against Gram-negative bacteria (E. coli, and P. aeruginosa) and Gram-positive bacteria (B. amyloliquefaciens and S. aureus), especially PEI1200-C6 showed the strongest antimicrobial activity with good biocompatibility at the MIC concentrations. Besides, PEI1200-C6 showed 4-16-fold better antibacterial effect than PEI1200, and fluorescent microscope imaging demonstrated that both of them could efficiently eradicate biofilms formed by four bacterial strains in vitro. As the accessible broad-spectrum antibacterial agents, PEI1200 and PEI1200-C6 are significant candidates to treat bacterial infections or eradicate biofilms on indwelling medical devices.

A Biomimetic Non-Antibiotic Approach to Eradicate Drug-Resistant Infections.

The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug-resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug-resistant strain. Here, a newly developed non-antibiotics based nanoformulation plus near-infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug-resistant pneumonia. The novel formulation contains 50-100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate-lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near-infrared-light-induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever-threatening drug-resistant infectious diseases when known antibiotics have failed.