ROS Scavenging and inflammation-directed polydopamine nanoparticles regulate gut immunity and flora therapy in inflammatory bowel disease.

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. STATEMENT OF SIGNIFICANCE: Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis.

Internal heating method of loop-mediated isothermal amplification for detection of HPV-6 DNA.

Loop-mediated isothermal amplification (LAMP) is a promising diagnostic tool for genetic amplification, which is known for its rapid process, simple operation, high amplification efficiency, and excellent sensitivity. However, most of the existing heating methods are external for completion of molecular amplification with possibility of contamination of specimens. The present research provided an internal heating method for LAMP using magnetic nanoparticles (MNPs), which is called nano-LAMP. Near-infrared light with an excitation wavelength of 808 nm was employed as the heating source; hydroxy naphthol blue (HNB) was used as an indicator to conduct methodological research. We demonstrate that the best temperature was controlled at a working power of 2 W and 4.8 µg/µL concentration of nanoparticles. The lowest limit for the detection of HPV by the nano-LAMP method is 102 copies/mL, which was confirmed by a gel electrophoresis assay. In the feasibility investigation of validated clinical samples, all 10 positive HPV-6 specimens amplified by nano-LAMP were consistent with conventional LAMP methods. Therefore, the nano-LAMP detection method using internal heating of MNPs may bring a new vision to the exploration of thermostatic detection in the future.

Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases.

Choroidal vascular diseases, such as age-related macular degeneration, are the leading cause of vision impairment and are characterized by pathological angiogenesis. Verteporfin-mediated photodynamic therapy is a current strategy that selectively occludes choroidal neovasculature. However, the clinically used large-dose systemic administration increases the risk of systemic adverse events, such as phototoxicity to superficial tissues. In this study, we developed an in situ verteporfin delivery system with a photoswitching synergistic function that disassembles in response to intraocular inflammatory enzymes. Under light-on conditions, verteporfin-mediated photodynamic therapy effectively occurs and this leads to vascular occlusion. Under light-off conditions, non-photoactive verteporfin negatively regulates vascular endothelial growth factor-induced angiogenesis as a yes-associated protein inhibitor. Taken together, our system serves as an intraocular verteporfin reservoir to improve the bioavailability of verteporfin by innovatively exploiting its photochemical and biological functions. This work provides a promising strategy with synergistic antiangiogenic effects for the treatment of choroidal vascular diseases.

Living Bacterial Hydrogels for Accelerated Infected Wound Healing.

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds and even serious tissue damage. Traditional treatments can not only kill pathogenic bacteria, but also suppress the growth of beneficial bacteria, thus destroying the balance of the damaged skin microbial ecosystem. Here, a living bacterial hydrogel scaffold is reported that accelerates infected wound healing through beneficial bacteria secreting antibacterial substances. Lactobacillus reuteri, a common probiotic, is encapsulated in hydrogel microspheres by emulsion polymerization and further immobilized in a hydrogel network by covalent cross-linking of methacrylate-modified hyaluronic acid. Owing to light-initiated crosslinking, the hydrogel dressing can be generated in situ at the wound site. This hydrogel scaffold not only protects bacteria from immune system attack, but also prevents bacteria from escaping into the local environment, thus avoiding potential threats. Both in vitro and in vivo experiments show that it has excellent ability against harmful bacteria and anti-inflammatory capabilities, promoting infected wound closure and new tissue regeneration. This work may open up new avenues for the application of living bacteria in the clinical management of infected wounds.

Glucose oxidase-mediated tumor starvation therapy combined with photothermal therapy for colon cancer.

Colon cancer is one of the most common cancers with high mortality, and can easily spread and metastasize, remaining an urgent disease to be solved. Nanomaterial-associated starvation or photothermal therapy has been considered to be a promising strategy in tumor therapy. However, the therapeutic effect of a single regimen for cancer treatment still needs to be improved due to their respective limitations. Herein, a biomimetic multifunctional nanoreactor is developed by encapsulating glucose oxidase and gold nanorods (AuNRs) in an erythrocyte membrane camouflaged metal-organic framework (MOF) nanoparticle (ZGAM), which was exploited for synergistic treatment of colon cancer by combining glucose oxidase-based starvation with AuNR-based photothermal therapy (PTT). This biomimetic nanoreactor could not only exhaust endogenous glucose to suppress the growth of the tumor by the released glucose oxidase (GOx), but also enhance the effect of photothermal therapy via inhibiting the expression of heat shock protein (HSP). In vitro and in vivo investigations indicate that this biomimetic nanoreactor shows excellent therapeutic effects on tumors, resulting from the synergistic treatment of starvation therapy and PTT. Therefore, the proposed strategy may open a window to develop an intelligent therapeutic system for better therapeutic efficacy against cancer.

Bioinspired oral delivery of gut microbiota by self-coating with biofilms.

Transplanting beneficial bacteria to the gut microbiome can positively modulate the bacterial composition and remains of great interest in prevention and treatment. However, environmental assaults and rapid transit times in the gastrointestinal (GI) tract result in low oral bioavailability and limited intestinal colonization. Here, we describe a bioinspired strategy of self-coating with biofilms that endows the transplanted gut microbiota with superior resistance and adhesion capacity. Using clinical Bacillus subtilis as a model probiotic bacterium, biofilm-coated probiotics demonstrate substantially improved GI tract tolerance and mucoadhesion in mice and swine. In particular, coated probiotics exhibit a 125-fold higher oral bioavailability and a 17 times greater intestinal colonization than uncoated bacteria in the porcine model. With notable ability to survive and reside in the GI tract, coated bacteria further show a significantly enhanced decolonization effect in mice colonized with Staphylococcus aureus. Self-coating with biofilms suggests a robust platform for oral doses of gut microbiota.

Switching between Elasticity and Plasticity by Network Strength Competition.

Switching a material between highly elastic and plastic would be of great use in many fields but has proven to be extremely challenging. Here, the use of mechanical strength competition between two networks in a hybrid material is reported to switch between elasticity and plasticity. In a gel material composed of an elastic polymer network and a shear-thinning nanofiber network, the excellent elasticity of the gel is demonstrated when the former is stronger than the latter. In contrast, the gel exhibits an extraordinary plasticity, which can be stretched to form a permanent anisotropic and tough gel due to the orientation of the nanofibers. The mechanical strength of each network can be simply tuned by adjusting either the crosslinking density or the loading of the nanofibers. This work may open a window to transform a material between superior elastic and plastic, which is useful for the development of adaptable materials.

Mechanical Deformation Mediated Transmembrane Transport.

Transmembrane transport is essential and plays critical roles for molecule exchange for cell survival. Methods capable of mimicking and regulating transmembrane transport have transformed the ability to create biosensors, separation membranes, and drug carriers. However, artificial channels have been largely restricted by their complicated chemical fabrication and inefficiency to dynamically manipulate the transport process. Here, a novel approach to regulate transmembrane transport is described by simply adjusting the mechanical deformation of liposomal bilayers which are covalently embedded in a crosslinked hydrogel network. This new approach is able to dynamically control transmembrane transport by stretching and loosening. The transmembrane diffusion of molecules can be switched on and off, and precisely tuned by varying strain. A potential of this method to programmably regulate cell growth is demonstrated by tuning external mechanical force. Given its unique characteristics, this method allows the development of innovative systems for controlled transmembrane transport of molecules.

Visible light controls cell adhesion on a photoswitchable biointerface.

Bioactive surfaces with specific interactions with cells have been greatly interested due to their potential applications in biosensors and tissue engineering. Herein, we fabricated a dopamine contained photoswitch molecule (compound 1) which could form self-assembled monolayer (SAM) on substrates. The SAM showed a good photoswitch ability and manifested excellent fatigue resistance, which displayed its potential application as a biologically friendly surface coating. Contact angle analysis and cell experiments exhibited that the SAM surface was hydrophobic before irradiation which favored cell adhesion, while, it turned hydrophilic and induced cell unfouling or detachment after light irradiation. The uses of visible light stimulation (λex = 530 nm) and the reversible regulation on cell adhesion and detachment should open up new avenues for bioacitve surfaces in biomedical applications.