Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Manipulating the Piezoelectric Response of Amino Acid-Based Assemblies by Supramolecular Engineering.

Variation in the molecular architecture significantly affects the electronic and supramolecular structure of biomolecular assemblies, leading to dramatically altered piezoelectric response. However, relationship between molecular building block chemistry, crystal packing and quantitative electromechanical response is still not fully understood. Herein, we systematically explored the possibility to amplify the piezoelectricity of amino acid-based assemblies by supramolecular engineering. We show that a simple change of side-chain in acetylated amino acids leads to increased polarization of the supramolecular arrangements, resulting in significant enhancement of their piezoelectric response. Moreover, compared to most of the natural amino acid assemblies, chemical modification of acetylation increased the maximum piezoelectric tensors. The predicted maximal piezoelectric strain tensor and voltage constant of acetylated tryptophan (L-AcW) assemblies reach 47 pm V-1 and 1719 mV m/N, respectively, comparable to commonly used inorganic materials such as bismuth triborate crystals. We further fabricated an L-AcW crystal-based piezoelectric power nanogenerator that produces a high and stable open-circuit voltage of over 1.4 V under mechanical pressure. For the first time, the illumination of a light-emitting diode (LED) is demonstrated by the power output of an amino acid-based piezoelectric nanogenerator. This work presents the supramolecular engineering toward the systematic modulation of piezoelectric response in amino acid-based assemblies, facilitating the development of high-performance functional biomaterials from simple, readily available, and easily tailored building blocks.

Self-Assembling Peptide-Based Functional Biomaterials.

Peptides can self-assemble into various hierarchical nanostructures through noncovalent interactions and form functional materials exhibiting excellent chemical and physical properties, which have broad applications in bio-/nanotechnology. The self-assembly mechanism, self-assembly morphology of peptide supramolecular architecture and their various applications, have been widely explored which have the merit of biocompatibility, easy preparation, and controllable functionality. Herein, we introduce the latest research progress of self-assembling peptide-based nanomaterials and review their applications in biomedicine and optoelectronics, including tissue engineering, anticancer therapy, biomimetic catalysis, energy harvesting. We believe that this review will inspire the rational design and development of novel peptide-based functional bio-inspired materials in the future.

NIR-Actuated Remote Activation of Ferroptosis in Target Tumor Cells through a Photothermally Responsive Iron-Chelated Biopolymer Nanoplatform.

Ferroptosis is a new form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies, and it would be of clinical significance to develop ferroptosis-inducing strategies with improved tumor specificity and modulability. Here we report a polydopamine-based nanoplatform (FeII PDA@LAP-PEG-cRGD) for the efficient loading of Fe2+ and ß-lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near-infrared light. PDA nanostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis-inducing Fe2+ ions. The NIR-actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released ß-lapachone and enhance intracellular H2 O2 formation to promote the Fe2+ -mediated lipid peroxidation.

Interface-Hybridization-Enhanced Photothermal Performance of Polypyrrole/Polydopamine Heterojunctions on Porous Nanoparticles.

Photothermal conversion agents (PTCAs) based on π-conjugated polymers are promising for cancer therapy, but the alteration of bandgap energies toward boosted photothermal properties remains challenging. Herein, polymer PTCAs with heterojunctions of a binary optical component are developed by interface hybridization on porous particles. Specifically, polypyrrole (PPy) nanodomains are successfully hosted on the wet-adhesive surface of mesoporous polydopamine nanoparticles through the loading and polymerization of pyrrole in the confined pore space (≈5.0 nm). The near-infrared absorbing polymers in the heterojunctions possess similar five-membered heterocyclic rings and can interact mutually to generate photoinduced electron transfer (PET). Such a large-area optoelectronic interaction progressively reduces the bandgap energy (down to 0.56 eV) by increasing the doped amount of PPy, which consequently enhances the extinction coefficient and photothermal conversion efficiency by 4.6- and 2.2-fold, respectively. Notably, the hybrid PTCA exhibits good biocompatibility, photocytotoxicity, and great potential for cancer therapy.

Fabrication of enzyme-responsive composite coating for the design of antibacterial surface.

In this study, a type of bacteria enzyme-triggered antibacterial surface with a controlled release of Ag ions was developed. Firstly, chitosan-silver nanocomposites (Chi@Ag NPs) were in situ synthesized via using ascorbic acid as reducing agent. Chi@Ag NPs were characterized by transmission electron microscopy, ultraviolet-visible spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Subsequently, Chi@Ag NPs and hyaluronic acid (HA) were used to fabricate antibacterial composite coating via Layer-by-Layer (LBL) self-assembly method. The successful construction of Chi@Ag NPs/HA composite coating was confirmed by scanning electron microscopy, energy dispersive spectroscopy and contact angle measurements, respectively. Then, the amount of released Ag ion was analyzed by inductively coupled plasma atomic emission spectrometry, which demonstrated that the release of Ag ions from the surface could be triggered by enzyme (e.g. hyaluronidase). A series of antibacterial tests in vitro, including zone of inhibition test, bacterial viability assay, antibacterial rate measurement and bacteria adhesion observation, demonstrated that the enzyme-responsive surface could inhibit the growth of bacteria. On the whole, this study provides an alternative approach for the fabrication of antibacterial surfaces on synthetic materials in various fields with the minimal side effects on surrounding environment and human body.

Fluorescent miRNA analysis enhanced by mesopore effects of polydopamine nanoquenchers.

The combination of fluorophore-labelled single-strand DNA probes and nanomaterial quenchers has shown great potential in miRNA detection. The development of advanced detection systems by understanding and controlling the fluorescence quenching/recovery via nanoquenchers' microstructures and local morphologies is an attractive area warranting further investigations. Inspired by nanopore sequencing, we present a novel miRNA sensing strategy using fluorophore-labeled DNA as probes and a type of large-pore-sized mesoporous polydopamine nanoparticles (MPDA-L, 70 nm in diameter) as fluorescence quenchers. It is revealed that the quenching efficiency of MPDA-L towards the fluorophore labelled on the probe, reached more than 99% at a relatively low particle concentration. Moreover, the mesopores effectively protected the probe DNA from cleavage by DNase I which was used for signal amplification. Sensitive detection of miRNA with a low detection limit of 32-40 pM, as well as a linear detection range of up to 5 nM, was realized by the mesopore effects via a greatly improved differential affinity of ssDNA and the probe-miRNA heteroduplex toward the surface of nanoquenchers. Interestingly, enhanced DLVO (Derjaguin-Landau-Verwey-Overbeek) repulsion generated inside the pore surface by the negative surface-curvature effect correlates with the improved duplex detachment and fluorescence recovery. The developed strategy can be successfully applied to quantify down-regulated let-7a and up-regulated miRNA-21 in different types of cancer cells by using total RNA samples from cell lysate. These findings are expected to inspire strategies and pave a way for utilizing porous nanomaterials for constructing miRNA detection systems.

Multifunctional Fe2O3@PPy-PEG nanocomposite for combination cancer therapy with MR imaging.

In recent years, magnetic hyperthermia nanoparticles have drawn great attention for cancer therapy because they have no limitation of tissue penetration during the therapy process. In this study, cubic nanoporous Fe2O3 nanoparticles derived from cubic Prussian blue nanoparticles were used as magnetic cores to generate heat by alternating the current magnetic field (AMF) for killing cancer cells. In addition, polypyrrole (PPy) was coated on the surfaces of the cubic Fe2O3 nanoparticles to load doxorubicin hydrochloride (DOX). The PEG component was then physically adsorbed onto the surfaces of the nanoparticles, resulting in a Fe2O3@PPy-DOX-PEG nanocomposite. The nanocomposite was triggered by acid stimulus and AMF to release DOX, resulting in a remarkable combination therapeutic effect via chemotherapy and magnetic hyperthermia. Furthermore, the nanocomposite could realize magnetic resonance imaging (MRI) due to the magnetic core structure. The study provides an alternative for the development of new nanocomposites for combination cancer therapy with MR imaging in vivo.

Surface modification of titanium substrates with silver nanoparticles embedded sulfhydrylated chitosan/gelatin polyelectrolyte multilayer films for antibacterial application.

To develop Ti implants with potent antibacterial activity, a novel "sandwich-type" structure of sulfhydrylated chitosan (Chi-SH)/gelatin (Gel) polyelectrolyte multilayer films embedding silver (Ag) nanoparticles was coated onto titanium substrate using a spin-assisted layer-by-layer assembly technique. Ag ions would be enriched in the polyelectrolyte multilayer films via the specific interactions between Ag ions and -HS groups in Chi-HS, thus leading to the formation of Ag nanoparticles in situ by photo-catalytic reaction (ultraviolet irradiation). Contact angle measurement and field emission scanning electron microscopy equipped with energy dispersive X-ray spectroscopy were employed to monitor the construction of Ag-containing multilayer on titanium surface, respectively. The functional multilayered films on titanium substrate [Ti/PEI/(Gel/Chi-SH/Ag) n /Gel] could efficiently inhibit the growth and activity of Bacillus subtitles and Escherichia coli onto titanium surface. Moreover, studies in vitro confirmed that Ti substrates coating with functional multilayer films remained the biological functions of osteoblasts, which was reflected by cell morphology, cell viability and ALP activity measurements. This study provides a simple, versatile and generalized methodology to design functional titanium implants with good cyto-compatibility and antibacterial activity for potential clinical applications.

Recyclable heparin and chitosan conjugated magnetic nanocomposites for selective removal of low-density lipoprotein from plasma.

A new fabrication protocol is described to obtain heparin and chitosan conjugated magnetic nanocomposite as a blood purification material for removal of low-density lipoprotein (LDL) from blood plasma. The adsorbent could be easily separated with an external magnet for recyclable use since it had a magnetic core. The LDL level of plasma decreased by 67.3 % after hemoperfusion for 2 h. Moreover, the adsorbent could be recycled simply washing with NaCl solution. After eight cycles, the removal efficiency of the adsorbent was still above 50 %. The recyclable magnetic adsorbent had good blood compatibility due to the conjugation of heparin to the chitosan-coated magnetic nanocomposites. The fabricated magnetic adsorbent could be applied for LDL apheresis without side effects.

Bioinspired Amino Acid Based Materials in Bionanotechnology: From Minimalistic Building Blocks and Assembly Mechanism to Applications.

Inspired by natural hierarchical self-assembly of proteins and peptides, amino acids, as the basic building units, have been shown to self-assemble to form highly ordered structures through supramolecular interactions. The fabrication of functional biomaterials comprised of extremely simple biomolecules has gained increasing interest due to the advantages of biocompatibility, easy functionalization, and structural modularity. In particular, amino acid based assemblies have shown attractive physical characteristics for various bionanotechnology applications. Herein, we propose a review paper to summarize the design strategies as well as research advances of amino acid based supramolecular assemblies as smart functional materials. We first briefly introduce bioinspired reductionist design strategies and assembly mechanism for amino acid based molecular assembly materials through noncovalent interactions in condensed states, including self-assembly, metal ion mediated coordination assembly, and coassembly. In the following part, we provide an overview of the properties and functions of amino acid based materials toward applications in nanotechnology and biomedicine. Finally, we give an overview of the remaining challenges and future perspectives on the fabrication of amino acid based supramolecular biomaterials with desired properties. We believe that this review will promote the prosperous development of innovative bioinspired functional materials formed by minimalistic building blocks.

Piezoelectric Biomaterials Inspired by Nature for Applications in Biomedicine and Nanotechnology.

Bioelectricity provides electrostimulation to regulate cell/tissue behaviors and functions. In the human body, bioelectricity can be generated in electromechanically responsive tissues and organs, as well as biomolecular building blocks that exhibit piezoelectricity, with a phenomenon known as the piezoelectric effect. Inspired by natural bio-piezoelectric phenomenon, efforts have been devoted to exploiting high-performance synthetic piezoelectric biomaterials, including molecular materials, polymeric materials, ceramic materials, and composite materials. Notably, piezoelectric biomaterials polarize under mechanical strain and generate electrical potentials, which can be used to fabricate electronic devices. Herein, a review article is proposed to summarize the design and research progress of piezoelectric biomaterials and devices toward bionanotechnology. First, the functions of bioelectricity in regulating human electrophysiological activity from cellular to tissue level are introduced. Next, recent advances as well as structure-property relationship of various natural and synthetic piezoelectric biomaterials are provided in detail. In the following part, the applications of piezoelectric biomaterials in tissue engineering, drug delivery, biosensing, energy harvesting, and catalysis are systematically classified and discussed. Finally, the challenges and future prospects of piezoelectric biomaterials are presented. It is believed that this review will provide inspiration for the design and development of innovative piezoelectric biomaterials in the fields of biomedicine and nanotechnology.

Application of a calcium and phosphorus biomineralization strategy in tooth repair: a systematic review.

Biomineralization is a natural process in which organisms regulate the growth of inorganic minerals to form biominerals with unique layered structures, such as bones and teeth, primarily composed of calcium and phosphorus. Tooth decay significantly impacts our daily lives, and the key to tooth regeneration lies in restoring teeth through biomimetic approaches, utilizing mineralization strategies or materials that mimic natural processes. This review delves into the types, properties, and transformations of calcium and phosphorus minerals, followed by an exploration of the mechanisms behind physiological and pathological mineralization in living organisms. It summarizes the mechanisms and commonalities of biomineralization and discusses the advancements in dental biomineralization research, guided by insights into calcium and phosphorus mineral biomineralization. This review concludes by addressing the current challenges and future directions in the field of dental biomimetic mineralization.

Preparation of calcium phosphate ion clusters through atomization method for biomimetic mineralization of enamel.

Dental enamel is a mineralized extracellular matrix, and enamel defect is a common oral disease. However, the self-repair capacity of enamel is limited due to the absence of cellular components and organic matter. Efficacy of biomimetic enamel mineralization using calcium phosphate ion clusters (CPICs), is an effective method to compensate for the limited self-healing ability of fully developed enamel. Preparing and stabilizing CPICs presents a significant challenge, as the addition of certain stabilizers can diminish the mechanical properties or biosafety of mineralized enamel. To efficiently and safely repair enamel damage, this study quickly prepared CPICs without stabilizers using the atomization method. The formed CPICs were evenly distributed on the enamel surface, prompting directional growth and transformation of hydroxyapatite (HA) crystals. The study revealed that the mended enamel displayed comparable morphology, chemical composition, hardness, and mechanical properties to those of the original enamel. The approach of repairing dental enamel by utilizing ultrasonic nebulization of CPICs is highly efficient and safe, therefore indicating great promise.

Activation of the PPARγ/NF-κB pathway by A-MPDA@Fe3O4@PVP via scavenging reactive oxygen species to alleviate hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (IRI) is a common pathological process during hepatectomy and liver transplantation and the two primary reasons for hepatic IRI are reactive oxygen species (ROS)-mediated oxidative stress and excessive inflammatory responses. Herein, a novel antioxidant nanodrug (A-MPDA@Fe3O4@PVP) is prepared by employing L-arginine-doped mesoporous polydopamine (A-MPDA) nanoparticles as the carrier for deposition of ultra-small ferric oxide (Fe3O4) nanoparticles and further surface modification with polyvinylpyrrolidone (PVP). A-MPDA@Fe3O4@PVP not only effectively reduces the aggregation of ultra-small Fe3O4, but also simultaneously replicates the catalytic activity of catalase (CAT) and superoxide dismutase (SOD). A-MPDA@Fe3O4@PVP with good antioxidant activity can rapidly remove various toxic reactive oxygen species (ROS) and effectively regulate macrophage polarization in vitro. In the treatment of hepatic IRI, A-MPDA@Fe3O4@PVP effectively alleviates ROS-induced oxidative stress, reduces the expression of inflammatory factors, and prevents apoptosis of hepatocytes through immune regulation. A-MPDA@Fe3O4@PVP can further protect liver tissue by activating the PPARγ/NF-κB pathway. This multiplex antioxidant enzyme therapy can provide new references for the treatment of IRI in organ transplantation and other ROS-related injuries such as fibrosis, cirrhosis, and bacterial and hepatic viral infection.

How can vanillin improve the performance of lignocellulosic biomass conversion in an immobilized laccase microreactor system?

Gentle and effective pretreatment is necessary to produce clean lignocellulosic biomass-based fuels. Herein, inspired by the efficient lignin degradation in the foregut of termites, the microreactor system using immobilized laccase and recoverable vanillin was proposed. Firstly, the co-deposition coating of dopamine, hydrogen peroxide and copper sulfate was constructed for laccase immobilization and a high immobilization efficiency of 87.0% was obtained in 30 min. After storage for 10 days, 82.2% activity was maintained in the laccase-loaded microreactor, which is 210.0% higher than free laccase. In addition, 6% (w/w) vanillin can improve lignin degradation in the laccase-loaded microreactor without impairing laccase activity, leading to a 47.3% increment in cellulose accessibility. Finally, a high cellulose conversion rate of 88.1% can be achieved in 1 h with glucose productivity of 2.62 g L-1 h-1. These demonstrated that the appropriate addition of vanillin can synergize with immobilized laccase to enhance the conversion of lignocellulosic biomass.

Fabrication of a New Hyaluronic Acid/Gelatin Nanocomposite Hydrogel Coating on Titanium-Based Implants for Treating Biofilm Infection and Excessive Inflammatory Response.

Persistent inflammation caused by implant-associated biofilm infections has emerged as a significant clinical issue. While many methods have been developed to give implants great anti-biofilm benefits, the post-inflammatory microenvironment is frequently disregarded. Oxidative stress (OS) due to excessive reactive oxygen species (ROS) is considered to be one of the specific physiological signals of the inflammation microenvironment. Herein, ZIF-90-Bi-CeO2 nanoparticles (NPs) were incorporated into a Schiff-base chemically crosslinked hydrogel composed of aldehyde-based hyaluronic acid and gelatin. Through chemical crosslinking between polydopamine and gelatin, the hydrogel coating adhered to the Ti substrate. The modified Ti substrate gained multimodal antibacterial and anti-biofilm functions, which were attributed to the photothermal effect of Bi NPs, and the release of Zn ions and CeO2 NPs. Notably, CeO2 NPs endowed the system with dual-enzyme (SOD- and CAT-like) catalytic activities. In a rat implant-associated infection (IAI) model, the dual-functional hydrogel had a biofilm-removal ability and regulated OS and inflammatory responses to facilitate osseointegration. The photothermal therapy combined with a host inflammation-microenvironment regulation strategy might provide a novel treatment for biofilm infection and the accompanying excessive inflammation.

Regulation of localized corrosion of 316L stainless steel on osteogenic differentiation of bone morrow derived mesenchymal stem cells.

Localized corrosion has become a concerning issue in orthopedic implants as it is associated with peri-implant adverse tissue reactions and implant failure. Here, the pitting corrosion of 316 L stainless steels (316 L SSs) was initiated by electrochemical polarization to simulate the in vivo localized corrosion of orthopedic implants. The effect of localized corrosion on osteogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs) was systematically studied. The results suggest that pitting corrosion of 316 L SS reduced the viability, adhesion, proliferation, and osteogenic differentiation abilities of BMSCs, especially for the cells around the corrosion pits. The relatively high concentrations of metallic ions such as Cr3+ and Ni2+ released by pitting corrosion could cause cytotoxicity to the BMSCs. The inhomogeneous electrochemical environment resulted from localized corrosion could promote reactive oxygen species (ROS) generation around the corrosion pits and cause oxidative stress of BMSCs. In addition, localized corrosion could also electrochemically interact with the cells and lead to cell membrane depolarization. The depolarized cell membranes and relatively high levels of ROS mediated the degradation of the osteogenic capacity of BMSCs. This work provides new insights into corrosion-mediated cell function degeneration as well as the material-cell interactions.

Structurally dynamic self-healable hydrogel cooperatively inhibits intestinal inflammation and promotes mucosal repair for enhanced ulcerative colitis treatment.

Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/ß-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive ß-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl-l-glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.

Tuning the arrangement of lamellar nanostructures: achieving the dual function of physically killing bacteria and promoting osteogenesis.

Bacteria killing behavior based on physical effects is preferred for biomedical implants because of the negligible associated side effects. However, our current understanding of the antibacterial activity of nanostructures remains limited and, in practice, nanoarchitectures that are created on orthopedics should also promote osteogenesis simultaneously. In this study, tilted and vertical nanolamellar structures are fabricated on semi-crystalline polyether-ether-ketone (PEEK) via argon plasma treatment with or without pre-annealing. The two types of nanolamellae can physically kill the bacteria that come into contact with them, but the antibacterial mechanisms between the two are different. Specifically, the sharp edges of the vertically aligned nanolamellae can penetrate and damage the bacterial membrane, whereas bacteria are stuck on the tilted nanostructures and are stretched, leading to eventual destruction. The tilted nanolamellae are more desirable than the vertically aligned ones from the perspective of peri-implant bone regeneration. Our study not only reveals the role of the arrangement of nanostructures in orthopedic applications but also provides new information about different mechanisms of physical antibacterial activity.