Beyond dissolution: Xerostomia rinses affect composition and structure of biomimetic dental mineral in vitro.

Xerostomia, known as dry mouth, is caused by decreased salivary flow. Treatment with lubricating oral rinses provides temporary relief of dry mouth discomfort; however, it remains unclear how their composition affects mineralized dental tissues. Therefore, the objective of this study was to analyze the effects of common components in xerostomia oral rinses on biomimetic apatite with varying carbonate contents. Carbonated apatite was synthesized and exposed to one of the following solutions for 72 hours at varying pHs: water-based, phosphorus-containing (PBS), mucin-like containing (MLC), or fluoride-containing (FC) solutions. Post-exposure results indicated that apatite mass decreased irrespective of pH and solution composition, while solution buffering was pH dependent. Raman and X-ray diffraction analysis showed that the addition of phosphorus, mucin-like molecules, and fluoride in solution decreases mineral carbonate levels and changed the lattice spacing and crystallinity of bioapatite, indicative of dissolution/recrystallization processes. The mineral recrystallized into a less-carbonated apatite in the PBS and MLC solutions, and into fluorapatite in FC. Tap water did not affect the apatite lattice structure suggesting formation of a labile carbonate surface layer on apatite. These results reveal that solution composition can have varied and complex effects on dental mineral beyond dissolution, which can have long term consequences on mineral solubility and mechanics. Therefore, clinicians should consider these factors when advising treatments for xerostomia patients.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Novel biomimetic nanostructured lipid carriers for cancer therapy: preparation, characterization, and in vitro/in vivo evaluation.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance (ABC) occurs after repeated injections, without changing the immunologic profile, despite PEGylation which prolongs the circulation function. To overcome these problems, we designed a red blood cell-membrane-coated NLC (RBCm-NLC), which was round-like, with a particle size of 60.33 ± 3.04 nm and a core-shell structure. Its stability was good, the drug paclitaxel (PTX) release from RBCm-PTX-NLC was less than 30% at pH7.4 and pH6.5, and the integrity of RBC membrane surface protein was maintained before and after preparation. Additionally, in vitro assays showed that, with the RBCm coating, the cellular uptake of the NLC by cancer cells was significantly enhanced. RBCm-NLC can avoid recognition by macrophage cells and prolong circulation time in vivo. In S180 tumor-bearing mice, the DiR-labeled RBCm-NLC group showed a stronger fluorescence signal and longer retention in tumor tissues, indicating a prompt tumor-targeting effect and extended blood circulation. Importantly, RBCm-PTX-NLC enhanced the antitumor effect and extended the survival period significantly in vivo. In summary, biomimetic NLC offered a novel strategy for drug delivery in cancer therapy.

Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms.

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.

Bioinspired red blood cell membrane-encapsulated biomimetic nanoconstructs for synergistic and efficacious chemo-photothermal therapy.

Recently, the fabrication of nanotechnology-based co-delivery systems has garnered enormous interest for efficacious cancer therapy. However, these systems still face certain challenges such as codelivery of drugs with different chemistries, inadequate loading efficiency, immune rejection resulting in rapid clearance and substantially poor bioavailability in vivo. To address the challenges, we have developed a biomimetic and stable design based on bovine serum albumin (BSA) nanoparticles that are encapsulated with a hydrophilic photothermal agent, indocyanine green (ICG), as well as a hydrophobic agent, gambogic acid (GA), via the desolvation method. Furthermore, these nanoconstructs have been coated with the red blood cell membranes (RBCm), which exhibit pronounced long-term circulation in addition to avoiding premature leakage of drugs. RBCm-coated BSA nanoparticles show a higher affinity towards both GA and ICG (RmGIB NPs), resulting in high loading efficiencies of 24.3 ±â€¯1.2 % and 25.0 ±â€¯1.2 %, respectively. Moreover, the bio-efficacy investigations of these biomimetic constructs (RmGIB NPs) in cells in vitro as well as in tumor-bearing mice in vivo confirm augmented inhibition, demonstrating potential synergistic chemo-photothermal therapeutic efficacy. Altogether, we provide an efficient delivery platform for designing and constructing BSA nanovehicles toward synergistic and effective co-delivery of therapeutics.

A biomimetic MOF nanoreactor enables synergistic suppression of intracellular defense systems for augmented tumor ablation.

A homotypic cancer cell membrane camouflaged MOF-based nanoreactor with the photothermal-starvation effect has been developed for synergistic suppression of intracellular defensive systems for enhanced cancer treatment.

Genetically Engineered Plasma Membrane Nanovesicles for Cancer-Targeted Nanotheranostics.

A series of ligand-targeted nanosystems have been rapidly exploited to selectively deliver drug molecules to desired cell populations. The conjugation of protein ligands to the nanoparticle (NP) surface endows nanovehicles with active targeting properties. However, the nonspecific covalent coupling of protein ligands to nanocarriers may compromise the protein targeting due to the uncontrolled ligand orientation as well as the decline in ligand activity during linkage process. With this regard, biomimetic synthetic strategies are employed for the preparation of genetically engineered nanovesicles (GNV) from cellular plasma membrane with targeting moieties on the surface in a ligand-oriented manner. Herein, we introduce the biomimetic synthetic strategy and procedures for GNV preparation. This chapter may guide readers to design analogous NPs for cell-specific targeting by displaying particular protein probes (e.g., antibody, nanobody, and single-chain antibody) on the surface of GNVs.

Magnetoliposomes of mixed biomimetic and inorganic magnetic nanoparticles as enhanced hyperthermia agents.

Recently, liposomes have been explored as a potential solution to improve the biocompatibility and the colloidal stability of magnetic nanoparticles. Protocols have been developed for producing magnetoliposomes of magnetite nanoparticles obtained inorganically (MNPs). However, the biomimetic synthesis of magnetite using heterologous proteins from magnetotactic bacteria has become a real alternative to produce novel biomimetic magnetic nanoparticles (BMNPs). Among these, the BMNPs obtained in presence of MamC protein from Magnetococcus marinus MC-1 have been proposed as excellent candidates to be potentially used as drug nanocarriers and as hyperthermia agents. However, their colloidal stability still needs to be improved while maintaining their magnetic properties intact. One possibility explored in this manuscript is to form magnetoliposomes that contain BMNPs. Indeed, the protocols developed for producing magnetoliposomes of MNPs need to be tested and modified to be able to include BMNPs. In this context, a protocol has been developed to produce both magnetoliposomes filled with MNPs and/or BMNPs and their potential as hyperthermia agents was tested. In fact, for the first time, these two types of nanoparticles were mixed in different proportions to test the composition that would optimize such as behaviour as hyperthermia agents. Interestingly, it was observed that the hyperthermia behaviour of the magnetoliposomes greatly improved if they were filled with a mixture of MNPs and BMNPs. These results indicate that these magnetoliposomes display optimal characteristics to become a potential agent for hyperthermia and that the opening of those liposomes could be externally controlled by applying an alternate magnetic field.

Wet/Sono-Chemical Synthesis of Enzymatic Two-Dimensional MnO2 Nanosheets for Synergistic Catalysis-Enhanced Phototheranostics.

2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug-loading capacity, and excellent photothermal conversion. However, few studies report their "enzyme-like" catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one-step wet-chemical method is first proposed for protein-directed synthesis of 2D MnO2 nanosheets (M-NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono-chemical approach is introduced for surface functionalization of the M-NSs with high dispersity/stability as well as metal-cation-chelating capacity, which can not only chelate 64 Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn2+ for enhanced biosafety. Interestingly, the resulting M-NS exhibits excellent enzyme-like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well-designed M-NS can achieve effective photoacoustic-imaging-guided synergistic starvation-enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small-sized and ultrathin M-NSs, which will broaden the application of 2D nanomaterials.

Enzyme mimetic activities of spinel substituted nanoferrites (MFe2O4): A review of synthesis, mechanism and potential applications.

Recently, the intrinsic enzyme-like activities of some nanoscale materials known as "nanozymes" have become a growing area of interest. Nanosized spinel substituted ferrites (SFs) with general formula of MFe2O4, where M represents a transition metal, are among a group of magnetic nanomaterials attracting researchers' enormous attention because of their excellent catalytic performance, biomedical applications and capability for environmental remediation. Due to their unique nanoscale physical-chemical properties, they have been used to mimic the catalytic activity of natural enzymes such as peroxidases, oxidases and catalases. In addition, various nanocomposite materials based on SFs have been introduced as novel artificial enzymes. This review mainly highlights the synthetic approaches for newly developed SF-nanozymes and also the structural/experimental factors that are effective on the kinetics and catalytic mechanisms of enzyme-like reactions. SF-nanozymes have been found potentially capable of being applied in various fields such as enzyme-free immunoassays and biosensors for colorimetric detection of biological molecules. Therefore, the application of SF nanoparticles, as efficient enzyme mimetics have been detailed discussed.

Biomimetic Synthesis of Ag2 Se Quantum Dots with Enhanced Photothermal Properties and as "Gatekeepers" to Cap Mesoporous Silica Nanoparticles for Chemo-Photothermal Therapy.

Ag2 Se quantum dots (QDs) with near-infrared (NIR) fluorescence have been widely utilized in NIR fluorescence imaging in vivo because of their narrow bulk band gap and excellent biocompatibility. However, most of synthesis methods for Ag2 Se QDs are expensive and the reactants are toxic. Herein, a new protein-templated biomimetic synthesis approach is proposed for the preparation of Ag2 Se QDs by employing bovine serum albumin (BSA) as a template and dispersant. The BSA-templated Ag2 Se QDs (Ag2 Se@BSA QDs) showed NIR fluorescence with high fluorescence quantum yield (≈21.2 %), excellent biocompatibility and good dispersibility in different media. Moreover, the obtained Ag2 Se@BSA QDs exhibited remarkable photothermal conversion (≈27.8 %), which could be used in photothermal therapy. As a model application in biomedicine, the Ag2 Se@BSA QDs were used as "gatekeepers" to cap mesoporous silica nanoparticles (MSNs) by means of electrostatic interaction. By taking the advantages of NIR fluorescence and photothermal property of Ag2 Se@BSA QDs, the obtained MSN-DOX-Ag2 Se nanoparticles (MDA NPs) were employed as a nanoplatform for combined chemo-photothermal therapy. Compared with free DOX and MDA NPs without NIR laser, the laser-treated MDA NPs exhibited lower cell viability in vitro, implying that Ag2 Se@BSA QDs are highly promising photothermal agents and the MDA NPs are potential carriers for chemo-photothermal therapy.

Facile synthesis of hydroxyapatite nanoparticles mimicking biological apatite from eggshells for bone-tissue engineering.

A facile synthesis of hydroxyapatite (HAp) nanoparticles that mimicked biological apatite by utilizing eggshells as a bio-calcium precursor was presented via the hydrothermal method and with the assistance of cetyltrimethylammonium bromide for bone-tissue engineering. The synthesized HAp was characterized by the X-ray powder diffraction method, Fourier transform infrared spectroscopy, field emission scanning microscopy, energy-dispersive X-ray spectroscopy, and nitrogen adsorption-desorption isotherms. The HAp nanoparticles were produced in film and pellet forms to determine their biomineralization and protein adsorption through in vitro studies in simulated body fluids and minimum essential medium supplemented with fetal bovine serum, respectively. A pure HAp nanocrystalline phase with rod-shaped nanoparticles of 161 nm in mean length and 52 nm in mean diameter was produced. The HAp was revealed to be a carbonated HAp exhibiting A- and B- type CO32- substitutions with CO32- content of 2.14 ± 1.36 wt.%, trace amounts of some important elements (Mg, Na, and K), and Ca/P atomic ratio of 1.54, thereby confirming that the HAp resembled the biological apatite in terms of morphology, structure, and composition. The HAp showed high biomineralization capability with the quick release of a double layer of bone-like apatite after 3 days in SBF and extremely high protein adsorption with 1213 ± 178 µg of proteins adsorbed on the HAp surface after 24 h. The HAp material had high bioactivity and cell affinity (cell adhesion, spreading, and proliferation). Thus, it has potential as a biomaterial for fabrication of BTE scaffolds. To our knowledge, this article is the first detailed study on biological tests of the HAp material derived from eggshells.

Natural Product-Based Pesticide Discovery: Design, Synthesis and Bioactivity Studies of N-Amino-Maleimide Derivatives.

Natural products are an important source of pesticide discovery. A series of N-amino-maleimide derivatives containing hydrazone group were designed and synthesized based on the structure of linderone and methyllinderone which were isolated from Lindera erythrocarpa Makino. According to the bioassay results, compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg·mL−1. Furthermore, the results of antifungal tests indicated that most compounds exhibited much better antifungal activities against fourteen phytopathogenic fungi than linderone and methyllinderone and some compounds exhibited better antifungal activities than commercial fungicides (carbendazim and chlorothalonil) at 50 µg·mL−1. In particular, compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed 60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5 µg·mL−1 respectively. Furthermore, compound 17 was synthesized, which lacks N-substituent at maleimide and its poor antifungal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50 µg·mL−1 showed that the backbone structure of N-amino-maleimide derivatives containing hydrazone group was important to the antifungal activity.

Fabrication and characterisation of a novel biomimetic anisotropic ceramic/polymer-infiltrated composite material.

OBJECTIVE: To fabricate and characterise a novel biomimetic composite material consisting of aligned porous ceramic preforms infiltrated with polymer. METHOD: Freeze-casting was used to fabricate and control the microstructure and porosity of ceramic preforms, which were subsequently infiltrated with 40-50% by volume UDMA-TEGDMA polymer. The composite materials were then subjected to characterisation, namely density, compression, three-point bend, hardness and fracture toughness testing. Samples were also subjected to scanning electron microscopy and computerised tomography (Micro-CT). RESULTS: Three-dimensional aligned honeycomb-like ceramic structures were produced and full interpenetration of the polymer phase was observed using micro-CT. Depending on the volume fraction of the ceramic preform, the density of the final composite ranged from 2.92 to 3.36g/cm3, compressive strength ranged from 206.26 to 253.97MPa, flexural strength from 97.73 to 145.65MPa, hardness ranged from 1.46 to 1.62GPa, and fracture toughness from 3.91 to 4.86MPam1/2. SIGNIFICANCE: Freeze-casting provides a novel method to engineer composite materials with a unique aligned honeycomb-like interpenetrating structure, consisting of two continuous phases, inorganic and organic. There was a correlation between the ceramic fraction and the subsequent, density, strength, hardness and fracture toughness of the composite material.

Biomimetically engineered Amphotericin B nano-aggregates circumvent toxicity constraints and treat systemic fungal infection in experimental animals.

Biomimetic synthesis of nanoparticles offers a convenient and bio friendly approach to fabricate complex structures with sub-nanometer precision from simple precursor components. In the present study, we have synthesized nanoparticles of Amphotericin B (AmB), a potent antifungal agent, using Aloe vera leaf extract. The synthesis of AmB nano-assemblies (AmB-NAs) was established employing spectro-photometric and electron microscopic studies, while their crystalline nature was established by X-ray diffraction. AmB-nano-formulation showed much higher stability in both phosphate buffer saline and serum and exhibit sustained release of parent drug over an extended time period. The as-synthesized AmB-NA possessed significantly less haemolysis as well as nephrotoxicity in the host at par with Ambisome®, a liposomized AmB formulation. Interestingly, the AmB-NAs were more effective in killing various fungal pathogens including Candida spp. and evoked less drug related toxic manifestations in the host as compared to free form of the drug. The data of the present study suggest that biomimetically synthesized AmB-NA circumvent toxicity issues and offer a promising approach to eliminate systemic fungal infections in Balb/C mice.

Biomimetically inspired asymmetric total synthesis of (+)-19-dehydroxyl arisandilactone A.

Complex natural products are a proven and rich source of disease-modulating drugs and of efficient tools for the study of chemical biology and drug discovery. The architectures of complex natural products are generally considered to represent significant barriers to efficient chemical synthesis. Here we describe a concise and efficient asymmetric synthesis of 19-dehydroxyl arisandilactone A-which belongs to a family of architecturally unique, highly oxygenated nortriterpenoids isolated from the medicinal plant Schisandra arisanensis. This synthesis takes place by means of a homo-Michael reaction, a tandem retro-Michael/Michael reaction, and Cu-catalysed intramolecular cyclopropanation as key steps. The proposed mechanisms for the homo-Michael and tandem retro-Michael/Michael reactions are supported by density functional theory (DFT) calculation. The developed chemistry may find application for the synthesis of its other family members of Schisandraceae nortriterpenoids.

3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects.

Biomimetic membrane-conjugated graphene nanoarchitecture for light-manipulating combined cancer treatment in vitro.

We report that through facile lipid self-assembly, biomimetic membrane-conjugated mesoporous silica-coated graphene oxide is constructed as targeting nanocarrier toward efficient combination of photothermal therapy and chemotherapy. Impressively, the simple surface modification with folate-contained lipid bilayer allows the graphene-based nanoarchitecture above to be selectively internalized by tumor cells overexpressing relevant receptors. Compared to pure drug, 7-fold doxorubicin is delivered into tumor cells by the nanoarchitecture. After cellular internalization, upon near infrared light illumination, graphene oxide in the nanoarchitecture can convert light energy into heat to kill cancer cells partially. Simultaneously, hyperthermia will drive rapid release of doxorubicin from the nanoarchitecture above to further cause the death of more cancer cells. Thus, integrated cancer treatment with higher efficacy is achieved in vitro compared to that of individual therapy.

Pectin impacts cellulose fibre architecture and hydrogel mechanics in the absence of calcium.

Pectin is a major polysaccharide in many plant cell walls and recent advances indicate that its role in wall mechanics is more important than previously thought. In this work cellulose hydrogels were synthesised in pectin solutions, as a biomimetic tool to investigate the influence of pectin on cellulose assembly and hydrogel mechanical properties. Most of the pectin (60-80%) did not interact at the molecular level with cellulose, as judged by small angle scattering techniques (SAXS and SANS). Despite the lack of strong interactions with cellulose, this pectin fraction impacted the mechanical properties of the hydrogels through poroelastic effects. The other 20-40% of pectin (containing neutral sugar sidechains) was able to interact intimately with cellulose microfibrils at the point of assembly. These results support the need to revise the role of pectin in cell wall architecture and mechanics, and; furthermore they assist the design of cellulose-based products through controlling the viscoelasticity of the fluid phase.

Biomimetic Total Synthesis of Hyperjapones†A-E and Hyperjaponols†A and†C.

Hyperjapones A-E and hyperjaponols A-C are complex natural products of mixed aromatic polyketide and terpene biosynthetic origin that have recently been isolated from Hypericum japonicum. We have synthesized hyperjapones A-E using a biomimetic, oxidative hetero-Diels-Alder reaction to couple together dearomatized acylphloroglucinol and cyclic terpene natural products. Hyperjapone A is proposed to be the biosynthetic precursor of hyperjaponol C through a sequence of: 1) epoxidation; 2) acid-catalyzed epoxide ring-opening; and 3) a concerted, asynchronous alkene cyclization and 1,2-alkyl shift of a tertiary carbocation. Chemical mimicry of this proposed biosynthetic sequence allowed a concise total synthesis of hyperjaponol C to be completed in which six carbon-carbon bonds, six stereocenters, and three rings were constructed in just four steps.