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Neutrophil extracellular traps (NETs) formed by neutrophils are netlike scaffolds that mainly contain DNA and a variety of granule proteins. Many stimuli can lead to the NET formation through independent molecular pathways. Clinically, the abundance of NETs is correlated with poor tumor prognosis. The biological actions of NETs are complex and diverse, including promoting tumor progression, awakening the dormant cancer cells, and resulting in immunosuppression in support of tumor growth and metastasis. Therefore, NET‐associated pathological processes provide an important clue for both diagnostic imaging and alternative therapies for many kinds of cancers. In recent years, scientists' efforts have focused on developing novel imaging probes to visualize NETs and therapeutic strategies by degrading NETs or inhibiting its formation to block their pro‐tumoral functions. In this review, the development and evaluation of NETs‐targeted imaging and intervention progress for tumor therapy are focused on. [ABSTRACT FROM AUTHOR]

Manganese dioxide (MnO2) nanosheets with a well-defined 2D structure can serve as catalase (CAT) and superoxide dismutase (SOD) mimics and hold a high potential in regulating the oxidative stress of atopic dermatitis (AD). However, facile, time-saving, and scalable synthesis of high-activity MnO2 nanosheets is still challenging. Here, we report a one-step oxidative synthesis strategy of MnO2 nanosheets and explore its potential as CAT and SOD mimics to exert antioxidant functions. After further gelatinization by integrating MnO2 nanosheets into a poly-(ethylene glycol)-diacrylate (PEGDA) polymer (PGM hydrogel), the obtained PGM hydrogel, characterized by well-designed cross-linking density and moisture retention, retains high antioxidation and cytoprotection ability. In AD-bearing mouse models, the PGM hydrogel facilitates the recovery of the impaired mice skin, reducing the severity score, scratching numbers, epidermal thickness, and immune factors, including mast cells, IgE antibodies, and inflammatory cytokines IL-4 and IL-10. Such a simple and reliable approach paves the way for the scale synthesis of MnO2 nanosheets and its practical application as antioxidative and immunoregulation agents for AD therapy. [ABSTRACT FROM AUTHOR]

Treating chronic wounds requires transition from proinflammatory M1 to anti-inflammatory M2 dominant macrophages. Based on the role of tumor extracellular vesicles (tEVs) in regulating the phenotypic switching from M1 to M2 macrophages, we propose that tEVs may have a beneficial impact on alleviating the overactive inflammatory microenvironment associated with refractory wounds. On the other hand, as a nitric oxide donor, S-nitrosoglutathione (GSNO) can regulate inflammation, promote angiogenesis, enhance matrix deposition, and facilitate wound healing. In this study, a guar gum-based hydrogel with tEVs and GSNO was designed for the treatment of diabetic refractory wounds. This hybrid hydrogel was formed through the phenyl borate bonds, which can automatically disintegrate in response to the high reactive oxygen species (ROS) level at the site of refractory diabetic wounds, releasing tEVs and GSNO. We conducted a comprehensive evaluation of this hydrogel in vitro, which demonstrated excellent performance. Meanwhile, using a full-thickness excision model in diabetic mice, the wounds exposed to the therapeutic hydrogel healed completely within 21 days. The increased closure rate was associated with macrophage polarization and collagen deposition, accelerated fibroblast proliferation, and increased angiogenesis in the regenerating tissues. Therefore, this multifunctional hybrid hydrogel appears to be promising for clinical applications. [ABSTRACT FROM AUTHOR]

Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra-sensitive pH-responsive degradability and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1α/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1α /VEGF pathway timely while enhancing the MRI effect. Statement of Significance In this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway. [ABSTRACT FROM AUTHOR]

Recently, gold nanomaterials have attracted extensive attention due to their unique physical, chemical and biological properties. In this study, gold nanostars (GNSTs) were synthesized first and functionalized with polyethylene glycol (PEG) and polyethylenimine (PEI). We found that GNSTs and their derivatives can be used as radiofrequency (RF) sensitizers for hyperthermia due to their special star shaped structure. Secondly, a multi-functional tumor-targeting drug delivery system DOX/GNSTs–PEG/PEI–FA was constructed. Doxorubicin (DOX) was covalently conjugated onto GNSTs–PEG/PEI by the pH-sensitive hydrazone linkage, and folic acid (FA) was directly conjugated to excess amino groups by amidation reaction. The release profiles of DOX from GNSTs–PEG/PEI–FA showed a strong dependence on the environmental pH value. These in vitro and in vivo results revealed that this drug delivery system has FA tumor-targeting, pH-sensitive controlled release, RF induced hyperthermia and X-ray contrast imaging effects, demonstrating that DOX/GNSTs–PEG/PEI–FA can be used as a potential nano-platform for tumor theranostic applications. [ABSTRACT FROM AUTHOR]

Context: Functionalized single-walled carbon nanotubes (SWNT) with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as novel and more convenient carriers of small interfering RNA (siRNA). Objective: To utilize the unique capability of SWNT to be easily modified by functional groups and readily internalized by mammalian cells to bind, condense, stabilize siRNA and enhance its transfection efficiency. Methods: After SWNT were non-covalently functionalized by cationic DOTAP (SWNT–DOTAP), siRNA interacted with SWNT–DOTAP via static electricity (SWNT–DOTAP/siRNA). Subsequently, the size, zeta potential and morphology of SWNT–DOTAP/siRNA were analyzed. The optimal compression ratio and stability of siRNA were assessed by agarose gel electrophoresis. Furthermore, in prostate carcinoma PC-3 cells, RT-PCR, flow cytometry and sulforhodamine B assays were used to evaluate the silencing activity, transfection efficiency and cell proliferation, respectively. Results and discussion: The characteristics of SWNT–DOTAP, i.e. an average size of 194.49 nm, a zeta potential of 45.16 mV and lower cytotoxicity than Lipofectamine 2000, indicated that this vector was suitable for siRNA delivery. Moreover, after interaction with SWNT–DOTAP, siRNA of human telomerase reverse transcriptase was bound, condensed and stabilized. In PC-3 cells, SWNT–DOTAP/siRNA exhibited 82.6% silencing activity and 92% transfection efficiency. Furthermore, the complexes inhibited cell proliferation by 42.1%. Conclusion: SWNT–DOTAP may be a promising siRNA delivery vector for gene-based therapeutic applications in cancer. [ABSTRACT FROM AUTHOR]

Context: Single-walled carbon nanotubes (SWCNTs), an important class of artificial nanomaterials with unique physicochemical properties, were used as novel carriers of curcumin. Objective: Formulation and evaluation of curcumin-loaded SWCNTs systems for utilizing the curcumin's anticancer potential by circumventing conventional limitations of extremely low aqueous solubility and instability under physiological conditions, and combining SWCNTs photothermal therapy enabled by the strong optical absorbance of SWCNTs in the 0.8-1.4 μm resulting in excessive local heating. Methods: After functionalized SWCNTs were confirmed, they were conjugated with curcumin (SWCNT-Cur). Subsequently, the formulation was analyzed for size, zeta-potential and morphology. And the solubility, stability and release of curcumin were assessed using spectrofluorometer, and the solid state of the curcumin was determined using X-ray diffraction and UV spectroscopy. Furthermore, in PC-3 cells, photothermal response was further determined by irradiating laser after the antitumor effect of SWCNT-Cur was evaluated. Results and discussion: SWCNTs were functionalized, and subsequent SWCNT-Cur conjugates were found to possess an average size of 170.4 nm, a zeta potential of −12.5 mV and to significantly enhance the solubility and stability of curcumin, overcoming the barriers to adequate curcumin delivery. Moreover, curcumin in SWCNT-Cur was in an amorphous form and could be rapidly released. In PC-3 cells, improved inhibition efficacy was achieved by SWCNT-Cur compared with native curcumin. Meanwhile, the SWCNTs in SWCNT-Cur served not only as scaffolds but also as thermal ablation agents, further inhibiting PC-3 cell growth. Conclusion: SWCNT-Cur assemblies may provide a promising delivery system for curcumin for use in cancer therapy. [ABSTRACT FROM AUTHOR]