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Photodynamic therapy (PDT) has long been shown to be a powerful therapeutic modality for cancer. However, PDT is undiversified and has become stereotyped in recent years. Exploration of distinctive PDT methods is thus highly in demand but remains a severe challenge. Herein, an unprecedented 1+1+1>3 synergistic strategy is proposed and validated for the first time. Three homologous luminogens with aggregation-induced emission (AIE) characteristics were rationally designed based on a simple backbone. Through slight structural tuning, these far-red/near-infrared AIE luminogens are capable of specifically anchoring to mitochondria, cell membrane, and lysosome, and effectively generating reactive oxygen species (ROS). Notably, biological studies demonstrated combined usage of three AIE photosensitizers gives multiple ROS sources simultaneously derived from several organelles, which gives superior therapeutic effect than that from a single organelle at the same photosensitizers concentration. This strategy is conceptually and operationally simple, providing an innovative approach and renewed awareness of improving therapeutic effect through three-pronged PDT.

Large skin wound infections have high morbidity, which threaten the health of human beings severely. It is essential to develop new wound dressings that can block microbial invasion, eliminate bacteria effectively, adhere to wounds firmly, and have good biocompatibility. In this work, we designed a kind of polysaccharide gel (DLG) dressings with derma-like structure that had good wound care performances. With a facile penetration cross-linking method by the Schiff base reaction between oxidized hyaluronic acid solution and carboxymethyl chitosan solution with higher viscosity, a gradient porous structure was formed inside DLG to mimic the structure of derma, which was due to the simultaneous penetration and reaction processes between two viscous solutions. This derma-like structure endowed the gel dressings with the abilities of self-adhesion to wounds and barriers against bacteria. Through the introduction of cuttlefish juice and gentamycin, the modified gel dressings (DLG-GS) showed mild photothermal effects under the near infrared irradiation at the wavelength of 808 nm, which could reach and maintain the temperature of 45 °C. The mild heat could act together with gentamycin to produce a rapid bactericidal performance within 5 min. Meanwhile, the polysaccharide gel dressings had good biocompatibility. The in vivo anti-infection properties of DLG-GS was demonstrated by an animal model of infected full-thickness skin defect. This strategy provided a feasible solution for the prevention and treatment of infected large wounds. STATEMENT OF SIGNIFICANCE: Derma-like antibacterial gel dressings (DLG-GS) with high bacterial barrier ability, strong tissue adhesive property and good biocompatibility were constructed by a penetration cross-linking method. DLG-GS could eliminate bacterial infection within 5 min due to the rational combination of a mild photothermal effect and antibiotics. DLG-GS showed high anti-infection and wound healing properties in an animal model of infected full-thickness skin defect. This study provides a flexible and universal strategy for the development of antibacterial wound dressings.

New preparation methods of vectors are the key to developing the next generation of biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established to obtain low-toxicity and efficient bioreducible polyguanidines (mPEG

Blood-contacting catheters occupy a vital position in modern clinical treatment including but not limited to cardiovascular diseases, but catheter-related thrombosis associated with high morbidity and mortality remains a major health concern. Hence, there is an urgent need for functionalized catheter surfaces with superior hemocompatibility that prevent protein adsorption and thrombus formation. In this work, we developed a strategy for constructing a kind of polyphenol-amine coating on the TPU surface (TLA) with tannic acid and lysine

Photodynamic therapy (PDT) has attracted tremendous attention in the antitumor and antimicrobial areas. To enhance the water solubility of photosensitizers and facilitate their accumulation in the tumor/infection site, polymeric materials are frequently explored as delivery systems, which are expected to show target and controllable activation of photosensitizers. This review introduces the smart polymeric delivery systems for the PDT of tumor and bacterial infections. In particular, strategies that are tumor/bacteria targeted or activatable by the tumor/bacteria microenvironment such as enzyme/pH/reactive oxygen species (ROS) are summarized. The similarities and differences of polymeric delivery systems in antitumor and antimicrobial PDT are compared. Finally, the potential challenges and perspectives of those polymeric delivery systems are discussed.

The efficacy of cardiac regenerative strategies for myocardial infarction (MI) treatment is greatly limited by the cardiac microenvironment. The combination of reactive oxygen species (ROS) scavenging to suppress the oxidative stress damage and macrophage polarization to regenerative M2 phenotype in the MI microenvironment can be desirable for MI treatment. Herein, melanin nanoparticles (MNPs)/alginate (Alg) hydrogels composed of two marine‐derived natural biomaterials, MNPs obtained from cuttlefish ink and alginate extracted from ocean algae, are proposed. Taking advantage of the antioxidant property of MNPs and mechanical support from injectable alginate hydrogels, the MNPs/Alg hydrogel is explored for cardiac repair by regulating the MI microenvironment. The MNPs/Alg hydrogel is found to eliminate ROS against oxidative stress injury of cardiomyocytes. More interestingly, the macrophage polarization to regenerative M2 macrophages can be greatly promoted in the presence of MNPs/Alg hydrogel. An MI rat model is utilized to evaluate the feasibility of the as‐prepared MNPs/Alg hydrogel for cardiac repair in vivo. The antioxidant, anti‐inflammatory, and proangiogenesis effects of the hydrogel are investigated in detail. The present study opens up a new way to utilize natural biomaterials for MI treatment and allows to rerecognize the great value of natural biomaterials in cardiac repair., Natural melanin nanoparticles/alginate hydrogels are proposed to attenuate inflammation by scavenging harmful reactive oxygen species and promoting macrophage polarization to regenerative M2 phenotype in the MI region for cardiac repair.

Fused deposition modelling (FDM) is a commonly used 3D printing technology. The development of FDM materials was essential for the product quality of FDM. In this work, a series of polycaprolactone (PCL)-based composites for low-temperature FDM were developed. By melt blending technique, different ratios of starch were added into PCL to improve the performances of FDM, and the printability, tensile strength, rheological properties, crystallization behaviors and biological performances of the composites were studied. The PCL/starch composite had the best performance in FDM process with the starch ratio of 9 ph at 80–90 °C. The melting strength and solidification rate of PCL/starch composites were improved. The starch also increased the crystallization temperature, degree of crystallinity and crystallization rate of PCL/starch composites, while had no negative effects on the tensile strength of PCL. Due to the low printing temperature, various kinds of bioactive components were added into PCL/starch composites for preparation of antibacterial and biocompatible materials for FDM. The present work provides a new method to develop novel low-temperature FDM materials with various functions., Graphical abstract Image 1, Highlights • PCL/starch composites for low-temperature fused deposition modelling were developed. • The tensile strength, rheological properties and crystallization behaviors of PCL/starch composites were studied. • Bioactive components were added to functionalize the composites with antibacterial and biocompatible properties.

Cancer cells are well recognized by immunotolerance characteristics, which include low immunogenicity, weak antigen presentation, low T cell infiltration, and high expression of inhibitory receptors and cytokines. This typical mechanism allows cancer cells to easily avoid the attack by immune cells, resulting in immune escape. Due to unique properties, such as adjustable size, unique surface properties, and ease of modification, nanomaterials have shown great potential in the field of immunotherapy. In this review, we summarize several ways in which nanomaterials can enhance the immune response against tumor cells. Therefore, we presently discuss the potential mechanisms involved in the induction of immune response by a series of nanomaterials. As a result, we also propose the generation of more advanced and tumor-driven nanomaterials, as well as their potential applications in tumor immunotherapy. According to the route of tumor immunity, we have currently classified nanomaterials into three categories: (1) Nanomaterials with inherent immunoregulatory functions, (2) nanomaterials that, upon an exogenous response, trigger immunogenic cell death and/or enhance immune responses, and (3) nanomaterials that are used as delivery vehicles to unload other immune-activating molecules (e.g., chemical drugs, photosensitizers, proteins and DNA plasmids) to tumors or immune cells as well as immune-activating molecules that may enhance an immune response. Some natural or synthetic nanomaterials can inherently stimulate macrophage polarization and enhance immune response. As such, nanomaterials may polarize M2 macrophages into M1 macrophages by regulating the cellular phenotype, reversing the tumor immune microenvironment and, ultimately, improving an immune cell killing activity. Cytokines or compounds with immune stimulating functions can enhance an immune response by promoting the proliferation of immune cells such as T lymphocytes and NK cells. Moreover, some nanomaterials rely on their own electrical properties or responsiveness to the tumor microenvironment, leading to tumor cell immunogenic death and/or enhancing anti-tumor immune responses. Nanomaterials have been widely used in photothermal, magnetocaloric and radiation therapies as well as into other fields, due to their unique optical, electrical, and magnetic properties. Recently, it has been discovered that some of these properties may “switch” tumor cells from non-immunogenic to immunogenic cells (i.e., immunogenic cell death) and, consequently, enhance an anti-tumor immune response. Compared with an endogenous response that mostly relies on characteristics of the tumor microenvironment, rationally designed nanomaterials that are responsive to exogenous responses can more effectively enhance the immune response at the tumor site and then achieve a more precise and tractable treatment. Hence, here we introduce the notion of an enhanced immune response, dependent on the use of nanomaterials co-stimulated by exogenous responses such as near-infrared light response, magnetic field response and others. Lastly, some substances, such as drugs, photosensitizers, proteins, plasmids, are unable to elicit a robust immune response when used without a carrier. In addition, some agents can also cause tissue damage and/or local toxicity when solely used for treatment. Thus, these substances often need to be combined with nanomaterials to achieve high biological loads, targeted delivery, controllable release and other functions to safely and efficiently enhance the anti-tumor immune response. Nevertheless, current research on nanomaterial-based immunotherapy is still under development, and the translation for clinical application is still challenging. Therefore, advances in the development of innovative therapeutic nanomaterials will offer great potential for improving the effectiveness of immunotherapy.

Cancer immunotherapy provides an effective way to deal with cancer. Although immunotherapy strategies have shown encouraging therapeutic effects, the inherent limitations of immunotherapy, such as multiple tumor immune evasion methods, low response rate, and systemic toxicity, still hinder its clinical applications. In recent decades, nanomaterials have been considered promising in cancer immunotherapy since they can realize targeted delivery and interact with the immune system to induce or enhance the antitumor immune responses. Among them, organic/inorganic nanocomposites are ideal candidates for cancer immunotherapy since they could combine the advantages of both organic and inorganic components. Multifunctional organic/inorganic nanocomposites could help overcome the shortcomings of current cancer immunotherapy, and realize the combination of immunotherapy and other therapeutic strategies with synergistic antitumor effects. Herein, we review the recent progress of organic/inorganic nanocomposites designed for cancer immunotherapy. The immunotherapy strategies of nanocomposites are summarized from the perspective of achieving immune enhancement. The challenges of nanocomposites in cancer immunotherapy are also discussed.

Catheter-induced infection is a severe problem in clinical practice, which induces significant morbidity, mortality and treatment costs. Therefore, there is a great requirement for developing antibacterial surfaces of catheter materials. In the present study, we develop a strategy for constructing self-adaptive antibacterial surfaces with bacterium-triggered antifouling-bactericidal switching properties on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer coating with one hierarchical structure was readily constructed on the PU surface (PU-PQ-PEG), which was composed of poly[2-(dimethyl decyl ammonium)ethyl methacrylate] (PQDMAEMA) brushes as the bactericidal lower layer and polyethylene glycol (PEG) as the antifouling upper layer. The two layers were incorporated with Schiff base structures, which could be broken by the metabolism of bacteria. Under normal and mild infection conditions, PU-PQ-PEG showed excellent antifouling and biocompatible properties against proteins and bacteria. When serious infection occurred and bacteria colonized on the PU-PQ-PEG surface, the bacteria could trigger the self-adaptive antifouling-bactericidal switching of the surface. Furthermore, the self-adaptive antibacterial properties of PU-PQ-PEG were also confirmed by an in vitro circulating model to simulate hydrodynamic conditions. PU-PQ-PEG showed self-adaptive antibacterial performances both under static and hydrodynamic conditions. The results of animal experiments also demonstrated the in vivo anti-infection performance. The present work will provide a promising strategy for developing antibacterial surfaces of catheter materials with hemocompatibility.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Multifunctional antibacterial materials have great significance for treating biomedical device-associated infections (BAIs). In the present work, a facile and rational strategy was developed to produce dual-functional implants with antibacterial and osteointegration-promoting properties for the treatment of BAI. A titanium implant, as a representative demo of implants, was first functionalized with ethanediamine-functionalized poly(glycidyl methacrylate) (PGED) brushes. Then, low-molecular-weight quaternized polyethyleneimine (QPEI, a cationic antibacterial agent) and alendronate (ALN, a clinically used drug with high affinity for bone minerals) were covalently conjugated onto PGED brushes to produce dual-functional dental implants (Ti-AQ). The QPEI component imparted Ti-AQ with antibacterial abilities, and the ALN component could balance the cytotoxicity of a cationic antibacterial agent, improving the biocompatibility for osteoblast cells. The effective performances of anti-infection and osteointegration were demonstrated in a BAI animal model. The results indicated that Ti-AQ inhibited bacterial infection at the early stage and enhanced the osteointegration and biomechanical properties between the implants and bone tissues at the late stage. This study will provide one facile and universal strategy for the design and development of novel multifunctional antibacterial implants.

由多糖和多功能无机纳米颗粒组成的多糖基复合纳米材料在生物医学领域具有潜在的应用价值, 是一种有希望的候选材料. 本文介绍了多糖基复合纳米材料的优良性能及其在成像和治疗中的应用. 除了多糖和无机纳米颗粒这两部分的功能简单结合以外, 复合纳米材料还具有协同性能和功能. 最后, 我们讨论了多糖基复合纳米材料在潜在的临床应用中的挑战和前景.

Small interfering RNA (siRNA)-based therapeutics have the potential to treat a series of hereditary and acquired diseases. However, one serious obstacle for siRNA therapy is the lack of an efficient strategy to transport the siRNA to the targeted organ/cell with minimal toxicity. To take advantage of the good biocompatibility and degradability of natural polymers, and to understand how the peptide sequence affects the properties of the vector, four biomimetic vectors (D10-K3H7, D10-R3H7, D20-K3H7, and D20-R3H7) were designed and synthesized by conjugating the peptide (K3H7 or R3H7) and dextran with a molecular weight of 10 or 20 kDa. Taking the commercial cellular transfection reagent Lipofectime RNAiMAX as a control, dextran-peptide/siRNA complexes exhibited smaller particle sizes, lower ζ potentials, and lower toxicity with the same value of N/P ratio. To evaluate the potential of this system for therapeutics, siRNA targeting the mRNA of the PCSK9 gene was chosen as a gene drug model to knock down the PCSK9 expression in the HepG2 cell line. Dextran-peptide/siRNA complexes exhibit a more consistent and higher knockdown efficiency than Lipofectamine RNAiMAX/PCSK9 siRNA complexes in a medium with 20% fetal bovine serum (FBS). D20-R3H7/PCSK9 siRNA complexes could knock down the level of PCSK9 mRNA by 85.2%, and they demonstrated a higher efficiency than Lipofectamine RNAiMAX, having 70.5% knockdown in the medium with 20% FBS at the PCSK9 siRNA concentration of 100 nM. These results suggest that the dextran-peptide-based vector has more efficient therapeutic agent properties for a siRNA-based drug transporter.

In recent years, traditional antibiotic efficacy has rapidly diminished due to the advent of multidrug-resistant (MDR) bacteria, which poses severe threat to human life and globalized healthcare. Currently, the development cycle of new antibiotics cannot match the ongoing MDR infection crisis. Therefore, novel strategies are required to resensitize MDR bacteria to existing antibiotics. In this study, novel cationic polysaccharide conjugates Dextran-graft-poly(5-(1,2-dithiolan-3-yl)-N-(2-guanidinoethyl)pentanamide) (Dex-g-PSS

Optical imaging in the second near infrared region (NIR-II, 1000-1700 nm) provides higher resolution and deeper penetration depth for accurate and real-time vascular anatomy, blood dynamics, and function information, effectively contributing to the early diagnosis and curative effect assessment of vascular anomalies. Currently, NIR-II optical imaging demonstrates encouraging results including long-term monitoring of vascular injury and regeneration, real-time feedback of blood perfusion, tracking of lymphatic metastases, and imaging-guided surgery. This review summarizes the latest progresses of NIR-II optical imaging for angiography including fluorescence imaging, photoacoustic (PA) imaging, and optical coherence tomography (OCT). The development of current NIR-II fluorescence, PA, and OCT probes (i.e., single-walled carbon nanotubes, quantum dots, rare earth doped nanoparticles, noble metal-based nanostructures, organic dye-based probes, and semiconductor polymer nanoparticles), highlighting probe optimization regarding high brightness, longwave emission, and biocompatibility through chemical modification or nanotechnology, is first introduced. The application of NIR-II probes in angiography based on the classification of peripheral vascular, cerebrovascular, tumor vessel, and cardiovascular, is then reviewed. Major challenges and opportunities in the NIR-II optical imaging for vascular imaging are finally discussed.

Infections caused by multidrug resistant bacteria are still a serious threat to human health. It is of great significance to explore effective alternative antibacterial strategies. Herein, carbon-iron oxide nanohybrids with rough surfaces (RCF) are developed for NIR-II light-responsive synergistic antibacterial therapy. RCF with excellent photothermal property and peroxidase-like activity could realize synergistic photothermal therapy (PTT)/chemodynamic therapy (CDT) in the NIR-II biowindow with improved penetration depth and low power density. More importantly, RCF with rough surfaces shows increased bacterial adhesion, thereby benefiting both CDT and PTT through effective interaction between RCF and bacteria. In vitro antibacterial experiments demonstrate a broad-spectrum synergistic antibacterial effect of RCF against Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA). In addition, satisfactory biocompatibility makes RCF a promising antibacterial agent. Notably, the synergistic antibacterial performances in vivo could be achieved employing the rat wound model with MRSA infection. The current study proposes a facile strategy to construct antibacterial agents for practical antibacterial applications by the rational design of both composition and morphology. RCF with low power density NIR-II light responsive synergistic activity holds great potential in the effective treatment of drug-resistant bacterial infections.

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone-apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.

Hydrogels with improved mechanical properties can expand to a greater range of applications. The fabrication of conventional toughened hydrogels typically requires precise modifications, multiple components, and complex steps. Here, a straightforward "one-step" polymerization method for the in situ preparation of hydrogels in aqueous solutions, is reported. Inspired by polymerization-induced self-assembly (PISA), water-miscible monomers are copolymerized during the hydrogel fabrication; the growing blocks eventually form physical bridges thus providing a mechanism for effective energy dissipation. The rheological and mechanical properties are evaluated and the results reveal that this strategy can be an effective approach to design mechanically enhanced hydrogels for a wide range of applications.

It is of great significance to develop multifunctional gene carriers to achieve treatments with enhanced therapeutic effects in an inflammation-free manner. In this work, assembled micelles of polysaccharide were utilized for the biomineralization of calcium carbonate to produce one-dimensional Alg-CaCO3 nanoparticles. In order to introduce both functions of mild hyperthermia and gene transfection, polydopamine (PDA) coating was applied to conjugate cationic polymers on the surface of nanoparticles. The resultant ACDP nanohybrids exhibited enhanced performance as gene carriers under near infrared (NIR) light irradiation at a low power density. Meanwhile, the pH-responsive degradation of gene carriers could further promote gene release for better effectiveness. The enhanced gene therapy induces tumor cell apoptosis, which could prevent inflammatory responses. The feasibility of mild hyperthermia-enhanced gene therapy for tumor treatment was investigated in vitro and in vivo. In addition, dual-modal ultrasound (US) and photoacoustic (PA) imaging was also realized to monitor and guide the treatment processes. The current work provides a new avenue for the construction of multifunctional platform to realize cancer therapy with improved therapeutic effectiveness in an inflammation-free manner.

There is an increasing demand for developing new materials and approaches for rapid and sensitive detection of protease biomarkers. Herein, the poly(methacrylic acid) (PMAA) brushes were synthesized from silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and flexibly functionalized with different fluorescein-labeled peptides, serving as the substrates for protease assay. To facilitate the point-of-care detection of protease, polyacrylamide gel pad arrays were fabricated to allow permeation of fluorescein-labeled peptide fragments cleaved from the PMAA brushes. This experimental setup enables an on-chip protease assay with an adequate limit of detection (LOD) for detecting trypsin in a buffer solution (3.9 pM) or in serum (1.4 nM) and good specificity for differentiation of trypsin and chymotrypsin. By using this experimental setup, matrix metalloproteinase-2 and matrix metalloproteinase-9 can be detected with LODs of 2.5 nM and 3.3 nM, respectively. Moreover, by introducing an adamantine (Ad) motif to the side-chain of the peptide fragment and β-cyclodextrin (β-CD) groups to the gel pad matrix, a 2.2-fold lower LOD was achieved for the detection of trypsin (1.8 pM) due to the supramolecular self-assembly of Ad and β-CD. Given the advances in the ease of sample handling, this rational design of peptide-functionalized PMAA brushes could be useful for on-chip detection of protease biomarkers or the screening of potential protease inhibitors.

It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass‐derived multilayer‐structured absorbable microparticles (MQxTy) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer‐by‐layer assembly. MQxTy microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQxTy microparticles with distinct Q+/T− double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous‐bone‐defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof‐of‐concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass‐based multilayer‐structured microparticles are very promising biomedical materials for clinical use., Biomass‐derived multilayer‐structured hemostatic microparticles (MQ2T2) composed of starches and plant polyphenols are constructed to integrate the advantages of cationized amylopectin (with high viscosity), polyphenol (with unique properties in accelerating hemostasis), and multilayer structures (with favorable biodegradability), which can achieve effective (accelerated hemostasis and promoted bone repair) treatments of bone defects with intractable bleeding in mouse and beagle models.

Left ventricular hypertrophy and fibrosis are major risk factors for heart failure, which require timely and effective treatment. Genetic therapy has been shown to ameliorate hypertrophic cardiac damage. In this study, it is found that in mice, the dopamine D5 receptor (D5R) expression in the left ventricle (LV) progressively decreases with worsening of transverse aortic constriction‐induced left ventricular hypertrophy. Then, a reversible treatment of left ventricular hypertrophy with Drd5 nucleic acids delivered by tobramycin‐based hyperbranched polyaminoglycoside (SS‐HPT) is studied. The heart‐specific increase in D5R expression by SS‐HPT/Drd5 plasmid in the early stage of left ventricular hypertrophy attenuates cardiac hypertrophy and fibrosis by preventing oxidative and endoplasmic reticulum (ER) stress and ameliorating autophagic dysregulation. By contrast, SS‐HPT/Drd5 siRNA promotes the progression of left ventricular hypertrophy and accelerates the deterioration of myocardial function into heart failure. The reduction in cardiac D5R expression and dysregulated autophagy are observed in patients with hypertrophic cardiomyopathy and heart failure. The data show a cardiac‐specific beneficial effect of SS‐HPT/Drd5 plasmid on myocardial remodeling and dysfunction, which may provide an effective therapy of patients with left ventricular hypertrophy and heart failure., Reversible treatments (deterioration or improvement) of pressure overload‐induced left ventricular hypertrophy and heart failure are readily achieved via one functional polyaminoglycoside vector (SS‐HPT) loaded with Drd5 siRNA (SS‐HPT/Drd5 siRNA) or Drd5 plasmid (SS‐HPT/Drd5 plasmid)

Gene editing is a crucial and effective strategy to treat genetic diseases. Safe and effective delivery vectors are specially required for efficient gene editing in vivo of CRISPR/Cas9 system. Interestingly, lactose, a natural saccharide, can specifically bind to asialoglycoprotein receptors, highly expressed on the surface of hepatocellular carcinoma (HCC) cells. Herein, a lactose‐derived branched cationic biopolymer (LBP) with plentiful reducible disulfide linkages and hydroxyl groups is proposed as a potential delivery vector of CRISPR/Cas9 system for efficient genome editing in vivo to treat orthotopic HCC. LBP is synthesized via a facile one‐pot ring‐opening reaction. LBP possesses excellent compacting ability, degradability, biocompatibility, gene transfection performances, and HCC‐targeting ability. LBP‐mediated delivery of classical pCas9‐survivin, which can target and knockout survivin oncogene, produces efficient gene editing performances, and superb anti‐cancer activities in orthotopic HCC mouse models. This study provides an attractive and safe strategy for the rational design of CRISPR/Cas9 delivery system., A polyhydroxy, reduction‐responsive degradable lactose‐derived branched cationic biopolymer is proposed as a safe and effective CRISPR/Cas9 delivery system for targeted therapy in orthotopic hepatocellular carcinoma.

With the development of biomedical materials, the widespread use of implantable medical devices such as biomedical catheters has saved lives and improved therapeutic outcomes in the clinic. Biomedical catheters (BCs) have the ability to connect the body inside and outside and are widely used in clinical sites for fluid discharging, blood indwelling, mechanical ventilating, and so on. However, catheter-related infections (CRIs) are common nosocomial infections with high morbidity and mortality. The pathogens in the urinary tract, blood, and lung tissue carried by BCs may be the direct cause of CRIs, and the bacterial biofilm on the surface of BCs provides a notable source of persistent diseases. Microcrystalline sulfamethoxazole (SMZ) and trimethoprim (TMP) were prepared in this study to increase both the specific surface area and water-solubility of antibacterial drugs, as well as to enhance the antibacterial and antifouling effects on the surface of BCs. As-prepared drugs and the excellent antifouling agent polyethylene glycol (PEG) were then used for the functionalization of BCs. The result indicated that the sizes of microcrystalline SMZ and TMP were 0.5-3 μm, 1-5 μm, respectively. The coating of BC-PEG-drugs exhibited excellent antibacterial efficacy in culture as well as preeminent antibacterial and antifouling abilities on the surface of BCs toward

Magnetic assemblies with special morphologies are promising for versatile biomedical applications due to their intriguing properties and performances. In this work, a polycation-functionalized bowl-shaped magnetic assembly (b-MNP-PGEA) was constructed for magnetic resonance imaging (MRI)-guided synergistic cancer therapy. Taking advantage of distinct properties of Fe3O4 nanoparticles, self-assembly concept, morphology control, and appropriate surface functionalization, the as-prepared magnetic assembly with special morphology was expected to work as a multifunctional carrier to realize the combination of magnetofection and photothermal therapy (PTT). The morphology effect of the magnetic assembly on cellular uptake and the subsequent gene transfection were investigated. The feasibility of the magnetic and photothermal carriers for MRI and complementary PTT/gene therapy was also studied. In addition, the excellent in vivo performance of the proposed bowl-shaped multifunctional carriers was demonstrated using a mouse breast cancer model. Interestingly, synergistic effects based on PTT-enhanced gene therapy were achieved. The facile assembly strategy for the development of special bowl-shaped magnetic carriers for synergistic PTT/gene therapy provides a new avenue for the versatile construction of efficient theranostic platforms.

Fluorescence-based theranostics provides a powerful platform for effective diagnosis and therapy. In particular, luminogens with aggregation-induced emission (AIE) characteristics have triggered state-of-the-art developments in theranostics, thanks to their intrinsic properties, including high signal-to-noise ratios, high photostability and capability as photosensitizing agents. However, the development of AIE luminogens for biological applications mostly stays at rational design and preparation through organic synthesis, which may give rise to high cost, environmental destruction and potential cytotoxicity. Actually, with easy access and good biocompatibility, it would be of great interest to employ AIE-active natural agents from herbs in theranostics and pharmacodynamics studies through fluorescence imaging. In this work, the use of berberine chloride, an AIE-active natural product from herbal plants, as a theranostic agent towards both cancer cells and bacteria is investigated. Through fluorescence bio-imaging, berberine chloride selectively targets cancer cells over normal cells and discriminates Gram-positive against Gram-negative bacteria. Furthermore, light-driven organelle-targeting migration of berberine chloride from mitochondria to the nucleus was discovered. Therapeutic evaluation shows that berberine chloride can efficiently ablate cancer cells over normal cells, and kill Gram-positive bacteria through both in vitro and in vivo photodynamic therapy. This work thus provides a blueprint for the next generation of theranostics using natural AIE luminogens.

The design of novel antibacterial materials has attracted increasing attention for combating bacterial infections. Herein, we conjugated zinc(ii) monoamino phthalocyanine (ZnMAPc) to poly(glycidyl methacrylate) (PGMA) via a ring-opening reaction, and the excess epoxy groups were scavenged by ethylenediamine (ED). The resultant macro-photosensitizer (PGED-Pc) can be easily dispersed in aqueous solution to form self-assembled nanoparticles and generate reactive oxygen species for inactivation of bacteria when exposed to light illumination. We found that the photodynamic pathway for the generation of singlet oxygen (1O2) was strongly inhibited in aqueous solution, and the major components for the inactivation of bacteria were superoxide anion radicals (˙O2-) and hydrogen peroxide (H2O2), which could result in the disruption of bacterial envelopes, the inactivation of vital enzymes, and the degradation of genomic DNA. PGED-Pc exhibited potent photodynamic antibacterial activity, with minimum bactericidal concentration (MBC, defined as 99.9% inactivation of bacteria) values of 128 μg mL-1 for Escherichia coli (E. coli) and 4 μg mL-1 for Staphylococcus aureus (S. aureus). As a proof-of-concept, the PGED-Pc nano-assemblies in aqueous solution can be readily immobilized on glass slides via a Schiff-base reaction, and impose potent photodynamic antibacterial activity upon light illumination. This work unveils a promising strategy for the engineering of self-sterilizing surfaces to combat bacterial infections.

Though the history of mankind, we are strongly fighting with infected diseases that are induced by bacteria, fungi, viruses, and other pathogens. Although a variety of medicines, including antibiotics and chemicals, have been developed since about one hundred years ago, many challenges are still threatening human health, such as drug resistance and emerging novel pathogens. Therefore, the development of antimicrobial materials has bloomed. From silver containers in ancient time to synthesized chemicals in the early 20th century, the antimicrobial materials are being improved to fight microorganisms. The efficacies of antimicrobial materials are further promoted by modern technologies. Recently, the efficacies and functions of antimicrobial materials are continuously enriched along with the advances of materials science and engineering, which strengthens the ability against complicated, severe infections and improves the performances on disease treatments. Multifunctional antimicrobial materials have drawn the greater attention of researchers. The multifunctional antimicrobial materials could not only fight against infections, but also promote the efficacy of medical devices, which will play significant roles in promoting the development of advanced medical devices. This review provides an overview on the development of multifunctional antimicrobial materials. The progress in applications of multifunctional antimicrobial materials is also summarized.

Organic/inorganic nanohybrids have attracted widespread interests due to their favorable properties and promising applications in biomedical areas. Great efforts have been made to design and fabricate versatile nanohybrids. Among different organic components, diverse polymers offer unique avenues for multifunctional systems with collective properties. This review focuses on the design, properties, and biomedical applications of organic/inorganic nanohybrids fabricated from inorganic nanoparticles and polymers. We begin with a brief introduction to a variety of strategies for the fabrication of functional organic/inorganic nanohybrids. Then the properties and functions of nanohybrids are discussed, including properties from organic and inorganic parts, synergistic properties, morphology-dependent properties, and self-assembly of nanohybrids. After that, current situations of nanohybrids applied for imaging, therapy, and imaging-guided therapy are demonstrated. Finally, we discuss the prospect of organic/inorganic nanohybrids and highlight the challenges and opportunities for the future investigations.

This work reports a study of electropolymerization kinetics, film thickness, stability, and antifouling properties of polydopamine (PDA) and its three analogues: poly(3-(3,4-dihydroxyphenyl)-l-alanine) (PL-DOPA), poly(5-hydroxytryptophan) (PL-5-HTP), and poly(Adrenalin) (PAdrenalin). It was observed that the number of the hydroxyl groups on the benzene ring and the type (primary vs secondary) of amine group significantly affect the electropolymerization kinetics and thus the thickness of the obtained polymer films. Monomers with two hydroxyl groups (except Adrenalin) resulted in films that were thicker (∼10-15 nm) than the one with only one hydroxyl group (PL-5-HTP) (∼5-8 nm) under similar conditions. Adrenalin containing a secondary amino group could not be deposited onto the ITO substrate, while the other three compounds containing a primary amino group completely covered the ITO. The PDA films had better electrochemical stability than the other films. No film showed stable antifouling surfaces against protein.

Multifunctional organic/inorganic nanocomposites are highly attractive for effective biomedical applications. In this work, versatile types of self-destructible polysaccharide (dextran or pullulan) nanocomposites (denoted Au@PSa) with adjustable amounts of unlockable Au nanorods (Au NRs) were fabricated as highly efficient photothermal cancer therapy systems. Taking advantage of the acidic endosomes and high concentration of glutathione (GSH) present in cancer cells, the responsive self-destruction of Au@PSa nanocomposites could unlock the abundant encapsulated Au NRs within cells. Notably, the pullulan-based nanocomposites (denoted Au@Pul) demonstrated liver cell-targeting properties, which could enhance the therapeutic effects while minimizing side effects. The strong absorption of the unlocked Au NRs in the near-infrared region was utilized to examine the photothermal performance. The Au@PSa nanocomposites with a moderate amount of Au NRs in the matrix exhibited very impressive photothermal effects in tumor therapy, where the encapsulated Au NRs were unlocked in the tumor region to realize the observed high performance. The proposed system could be further extended, as the polysaccharides were functionalized with amino groups. The current work provides a facile strategy to construct flexible therapeutic platforms with responsive self-destruction features. A strategy that relies on polysaccharides and gold nanorods to realize cancer therapy shows promise in live animal studies. In photothermal therapy, nanoparticles in cancerous tissue convert laser light into heat and damage tumors while leaving surrounding healthy tissue unharmed. Nana Zhao and Fu-Jian Xu from the Beijing University of Chemical Technology in China and colleagues synthesized polysaccharide-based nanocapsules that can encapsulate photothermal gold nanorods (pullulan-gold nanocomposites), and simultaneously target asialoglycoprotein receptor overexpressed liver cancer cells. Using real-time confocal laser scanning microscopy, the team demonstrated that the nanocomposites rapidly accumulated around the nuclei of hepatoma cells, where acidic conditions dissolved the polysaccharide matrix and unleashed gold nanorods with the assistance of glutathione. Images taken after photothermal therapy in mice revealed massive shrinking of cancerous cells and fragmented nuclei, with no side effects on major organs. Versatile types of self-destructible polysaccharide nanocomposites with adjustable amounts of unlockable Au nanorods were fabricated for highly efficient photothermal cancer therapy systems.

Safe and effective vectors play an important role in nucleic acid delivery processes. Ring-opening reactions are quite often used to produce biomaterials with various functions and properties. Instead of surface-conjugated hydrophilic polymers such as polyethylene glycol, uniformly-distributed hydroxyl groups within one polycation could improve biocompatibility and benefit nucleic acid delivery performances. Hydroxyl groups with uniform distribution are readily produced by ring-opening of O -heterocyclic units. O -Heterocyclic units include cyclic ester (epoxide), carbonate and lactones . Hydroxyl-rich polycationic systems are prepared predominately with aminated poly(glycidyl methacrylate) (PGMA). PGMA is the most common epoxy polymer and can be post-modified readily via epoxide ring-opening reactions by different amine species. Hydroxyl-rich polycationic systems are also reported by ring-opening polymerization between various epoxy and amine units. In addition, post hydroxylation of polycations via different O -heterocyclic ring-opening reactions could give rise to various hydroxyl-rich polycationic systems. More recently, versatile types of hydroxyl-rich polycationic systems with special molecular and topological structures, such as linear, star-shaped, comb-shaped, supramolecular, branched, hierarchical, and hetero-nanostructured carriers, are well studied. This review summarizes recent research activities in hydroxyl-rich polycationic systems. Their different design strategies via O -heterocyclic ring-opening reactions and unique nucleic acid delivery applications are described in detail. The research activities indicate that hydroxyl-rich polycationic systems become versatile and powerful candidates for the development of advanced multifunctional delivery systems of nucleic acids.

Colorectal cancer (CRC) is one of the most malignant cancers worldwide. Nonylphenol (NP) is an endocrine-disruptor chemical and plays an important role in the development of cancers. However, the effects of NP on CRC remain unclear. In this study, we aimed to investigate the potential mechanisms of NP in the pathogenesis of CRC.The levels of AhR, TL1A and HDAC2 in CRC tissues and endothelial cells were assessed by RT-qPCR or western blot. CHIP and dual luciferase reporter assays were used to confirm the interaction between AhR and HDAC2, or HNF4α and TL1A. The CCK8, would healing and tube formation assays were conducted to evaluate the proliferation, migration and angiogenesis of HUVECs. Western blot determined HNF4α protein and HNF4α acetylation levels. The secreted TL1A protein was detected by ELISA. The angiogenesis-related factor CD31 was tested by IHC.The expression level of AhR was significantly up-regulated in CRC tissues and endothelial cells. Moreover, NP activated the AhR pathway mediated colorectal endothelial cell angiogenesis and proliferation, while TL1A overexpression resisted these effects caused by NP. Besides, NP was found to modulate HNF4α deacetylation through AhR/HDAC2 to inhibit TL1A. Furthermore, in vivo experiments proved that NP regulated CRC growth and angiogenesis via AhR/HDAC2/HNF4α/TL1A axis.This study revealed that NP promoted CRC growth and angiogenesis through AhR/HDAC2/HNF4α/TL1A pathway and could be a new therapeutic target for CRC treatment.

The protumoral and immunosuppressive tumor microenvironments greatly limit the antitumor immune responses of nanoparticles for cancer immunotherapy. Here, the intrinsic immunomodulatory effects of orchestrated nanoparticles and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, are explored. By optimizing both the composition and morphology, a facile strategy is proposed to construct yolk-shell nanohybrids (Fe

Metastasis has been widely recognized as the most lethal threats for cancer patients. Due to their special genetic and environmental context, cancer stem cells (CSCs) which are resistant to most cytotoxic drugs and radiation, are considered as the dominant culprit for metastasis. Thus, the efficient targeting and thorough elimination of CSCs are significantly urgent for the enhancement of therapeutic efficacy. Herein, we developed a facile and smart photothermal-chemo therapeutic nano-assembly system, of which the surface was modified by a sheddable PEG shell and acid-activatable pro-penetration peptide, to surmount the physiological barriers in targeting CSCs. A highly-efficient diradical-featured croconium-based photothermal agent and a natural cytotoxic heat shock protein (HSP) inhibitor were co-loaded in redox-sensitive chitosan matrices to realize the synergistic photothermal-chemo therapy. Within solid tumors, the PEG shell that prevents the nano-assembly from mononuclear phagocytic clearance could rapidly leave to expose the positively charged chitosan, and the detached iRGD could further actuate the tumor penetration of chitosan nanoparticles, and allow the CSCs targeting by selective recognition of CD44 protein. Owing to the HSP inhibition and chemo-sensitization, both the CSCs and non-CSCs could be thoroughly eliminated by the designed nano-assembly, largely inhibiting the tumor growth and metastasis. This work provides a potential strategy for CSCs-targeting drug delivery to solve the CSCs-related metastasis.

Effective hemostatic materials are very important for treating trauma cases. Natural polysaccharides have been particularly appealing in the development of new hemostatic materials due to their unique functions in human bodies. In this work, different polysaccharide-based hemostatic porous sponges (SHDP or SHDQ) of cross-linked hyaluronic acid (HA)/cationized dextran were readily prepared by the self-foaming process of HA and poly((2-dimethyl amino)-ethyl methacrylate)-grafted dextran (Dex-PDM) or partially-quaternized Dex-PDM in the presence of sodium trimetaphosphate crosslinkers. SHDP and SHDQ sponges were investigated in terms of liquid-absorption ability, hemolysis, whole-blood clotting and hemostatic activity in hemorrhaging-liver models. Compared with HA/Dex-PDM sponges (HDP) without chemical cross-linking, SHDP and SHDQ sponges displayed higher porosity (>70.0% vs. 48.9%) and swelling ratios (>1000% vs. 520%). Meanwhile, hemolysis assay revealed the good blood compatibility of SHDP and SHDQ with low hemolysis ratio (below 0.5%). Furthermore, in vitro and in vivo hemostatic assay showed that SHDQ possessed better hemostatic properties than SHDP, owing to the higher cationic charges of partially-quaternized Dex-QPDM than Dex-PDM. The present study demonstrated that the self-foaming process of HA/Dex-PDM under a 'green' condition is an effective means to produce new hemostatic materials.

Bone defects represent a clinical challenge that severely impacts the quality of life of affected patients. To match the shape of a bone defect area exactly, additive manufacturing has emerged as a promising technology to produce customized bone regeneration scaffolds for bone defect treatment. In this study, new three-dimensional (3D)-printed poly(L-lactic acid) (PLLA)/hydroxyapatite (HA) composite scaffolds were developed. HA nanoparticles were first modified by a straightforward, economical method. Briefly, HA nanoparticles were modified with dopamine and hexamethylenediamine, and PLLA chains were grafted onto the HA nanoparticles by aminolysis reaction. Then, the PLLA-modified HA nanoparticles were blended with PLLA to form a thermoplastic composite for 3D printing. Due to the high compatibility between the PLLA matrix and PLLA-modified HA nanoparticles, the 3D-printed PLLA/HA scaffolds possess robust mechanical properties and good biocompatibility. This study provides a flexible strategy to fabricate scaffolds for the customized treatment of bone defects.

A zwitterionic poly(sulfobetaine-3,4-ethylenedioxythiophene) (PSBEDOT)-based glucose biosensor was fabricated via encapsulating glucose oxidase (GOx) in a one-step electropolymerization method. Integrating conductivity and hydrophilic properties, PSBEDOT provides a great framework for GOx immobilization and stabilization. The anti-fouling, high-sensitivity, and long-term stability properties of PSBEDOT–GOx make it a promising platform for long-term and continuous glucose monitoring.

Thoracic aortic dissection (TAD) is an aggressive and life-threatening vascular disease and there is no effective means of early diagnosis of dissection. Type IV collagen (Col-IV) is a major component of the sub-endothelial basement membrane, which is initially exposed followed by endothelial injury as early-stage event of TAD. So, we want to build a noninvasive diagnostic method to detect early dissection by identifying the exposed Col-IV via MRI. Methods Col-IV-targeted magnetic resonance/ fluorescence dual probe (Col-IV-DOTA-Gd-rhodamine B; CDR) was synthesized by amide reaction and coordination reaction. Flow cytometry analysis was used to evaluate the cell viability of SMC treated with CDR and fluorescence assays were used to assess the Col-IV targeting ability of CDR in vitro. We then examined the sensitivity and specificity of CDR at different stages of TAD via MRI and bioluminescence imaging in vivo. Results The localization of Col-IV (under the intima) was observed by histology images. CDR bound specifically to Col-IV-expressing vascular smooth muscle cells and BAPN-induced dissected aorta. The CDR signal was co-detected by magnetic resonance imaging (MRI) and bioluminescence imaging as early as 2 weeks after BAPN administration (pre-dissection stage). The ability to detect rupture of dissected aorta was indicated by a strong normalized signal enhancement (NSE) in vivo. Moreover, NSE was negatively correlated with the time of dissection rupture after BAPN administration (r2 = 0.8482). Conclusion As confirmed by in vivo studies, the CDR can identify the exposed Col-IV in degenerated aorta to monitor the progress of aortic dissection from the early stage to the rupture via MRI. Thus, CDR-enhanced MRI proposes a potential method for dissection screening, and for monitoring disease progression and therapeutic response.