Bifunctionalized mesoporous silicasupported gold nanoparticles as oxidase and peroxidase mimics for antibacterial applications are demonstrated. For the first time, these mesoporous silica‐supported ...gold nanoparticles are applied as oxidase and peroxidase mimics. Taking advantage of their prominent enzyme activities, the MSN‐AuNPs show excellent antibacterial properties against both Gram‐negative and Gram‐positive bacteria. Furthermore, MSN‐AuNPs also exhibit outstanding performance in biofilm elimination .
Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to ...generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO
. By adjusting the ratio of reactants, highly-ordered MnO
@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO
functions as catalase mimic. In this way, the well-defined MnO
@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.
Graphitic carbon nitride (g‐C3N4) has been used as photosensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its therapeutic efficiency was far from ...satisfactory. One of the major obstacles was the overexpression of glutathione (GSH) in cancer cells, which could diminish the amount of generated ROS before their arrival at the target site. Herein, we report that the integration of Cu2+ and g‐C3N4 nanosheets (Cu2+–g‐C3N4) led to enhanced light‐triggered ROS generation as well as the depletion of intracellular GSH levels. Consequently, the ROS generated under light irradiation could be consumed less by reduced GSH, and efficiency was improved. Importantly, redox‐active species Cu+–g‐C3N4 could catalyze the reduction of molecular oxygen to the superoxide anion or hydrogen peroxide to the hydroxyl radical, both of which facilitated the generation of ROS. This synergy of improved ROS generation and GSH depletion could enhance the efficiency of PDT for cancer therapy.
Looks like a job for a copper: The integration of Cu2+ with graphitic carbon nitride (g‐C3N4) nanosheets greatly improved the efficiency of these photosensitizers for photodynamic therapy. The observed improvement in cytotoxicity was due to the enhanced light‐triggered generation of reactive oxygen species in combination with the depletion of intracellular glutathione (GSH) levels (see picture).
Nanoparticulate delivery platforms have shown promising advantages for vaccines in many aspects. However, their application was limited so far by lengthy synthetic protocols, the requirement of ...specific modification of antigen, and by the low efficiency in inducing antigen‐specific cytotoxic T‐lymphocyte responses. This study demonstrates for the first time the construction of metal‐organic‐framework (MOF) based vaccines by encapsulating ovalbumin (OVA) and attaching the cytosine‐phosphate‐guanine oligodeoxynucleotides (CpG ODNs) in/on zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles. The pH responsive decomposition feature enables the system to release the protein antigens and CpG ODNs in the same antigen presenting cells more efficiently. More importantly, in addition to the induction of a potent immune memory response, both in vitro and in vivo experiments show that the vaccines can induce strong humoral and cellular immunity. These findings suggest that the MOF‐based vaccine platforms can be used to produce effective vaccines against a range of ailments, which will facilitate the application of MOFs in biomedical areas.
In this paper, metal‐organic‐framework (MOF) based vaccines are fabricated facilely to deliver protein antigens and adjuvants in the same antigen presenting cells. Both in vitro and in vivo experiments demonstrate that the nanocomposites can induce strong humoral, cellular immunity, and potent immune memory response. The MOF‐based vaccine platform can be useful for the prevention and/or therapy of various diseases.
mTORC1, a central controller of cell proliferation in response to growth factors and nutrients, is dysregulated in cancer. Whereas arginine activates mTORC1, it is overridden by high expression of ...cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1). Because cancer cells often encounter low levels of nutrients, an alternative mechanism might exist to regulate CASTOR1 expression. Here we show K29-linked polyubiquitination and degradation of CASTOR1 by E3 ubiquitin ligase RNF167. Furthermore, AKT phosphorylates CASTOR1 at S14, significantly increasing its binding to RNF167, and hence its ubiquitination and degradation, while simultaneously decreasing its affinity to MIOS, leading to mTORC1 activation. Therefore, AKT activates mTORC1 through both TSC2- and CASTOR1-dependent pathways. Several cell types with high CASTOR1 expression are insensitive to arginine regulation. Significantly, AKT and RNF167-mediated CASTOR1 degradation activates mTORC1 independent of arginine and promotes breast cancer progression. These results illustrate a mTORC1 regulating mechanism and identify RNF167 as a therapeutic target for mTORC1-dysregulated diseases.
Abstract New combination therapy strategy, which takes the advantages of co-delivery two or more therapeutic agents in one nanocarrier platform, has been widely used in the clinic and achieved ...immense popularity in cancer treatment. Here, we have rationally developed a multifunctional platform using a self-assembly strategy to incorporate materials with specific functions of chemotherapeutics, hyperthermia, and especially immunotherapy, which can collectively contribute to the effective cancer treatment. We design the immunomodulatory CpG ODNs based platform that is conjugated with NIR-responsive gold nanorods and doxorubicin for cancer therapy. The gold nanorods can be applied as the nanocarrier to simultaneously address the three kinds of treatments, which lead to a significant benefit relative to the use of each method alone. Both in vitro and in vivo assays reveal that this engineered vehicle exhibits significant antitumor efficacy. Our studies provide strong evidence that the AuNRs-CpG-Dox conjugates can be utilized as efficient antitumor agents.
A facile one‐pot synthesis of fluorescent AuNCs by using ovalbumin‐CpG oligodeoxynucleotides (ODNs) conjugates as the templates, which can elicit specific immunological responses, is demonstrated. ...Through dual‐delivery of protein antigen and CpG ODNs, the as‐prepared AuNCs can act as smart self‐vaccines to assist in generation of high immunostimulatory activity while simultaneously act as an imaging agent. The AuNCs‐based vaccines are not thought to have not been reported so far, making this platform the first example of the usage of AuNCs as effective vaccines. Furthermore, compared with the antigen, the immunostimulatory activity of the as‐prepared AuNCs can not only be retained, but also can be effectively enhanced. These findings suggest the AuNCs‐based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.
A facile one‐pot synthesis of fluorescent AuNCs by using ovalbumin‐CpG oligodeoxynucleotides (ODNs) conjugates as the templates, which can elicit specific immunological responses, is demonstrated. Through dual‐delivery of protein antigen and CpG ODNs, the as‐prepared AuNCs can act as smart self‐vaccines to assist in generation of high immunostimulatory activity while simultaneously act as an imaging agent.
Surface‐active artificial enzymes (SAEs) are designed and constructed by a general and novel strategy. These SAEs can simultaneously stabilize Pickering emulsions and catalyze biphasic ...biotransformation with superior enzymatic stability and good re‐usability; for example, for the interfacial conversion of hydrophobic p‐nitrophenyl butyrate into yellow water‐soluble p‐nitrophenolate catalyzed by esterase‐mimic SAE.
Herein, a new strategy has been developed through combining a microwave‐assisted technique with hydrothermal treatment to reduce graphene waste and improve production yield of graphene quantum dots ...(GQDs) prepared by top‐down methods. By using fluorinated graphene oxide (FGO) as a raw material, fluorinated GQDs and nonfluorinated GQDs can be synthesized. Additionally, in the fluorinated GQDs, the protective shell supplied by fluorine improves the pH stability of photoluminescence and the strong electron‐withdrawing group, F, reduces the π‐ electron density of the aromatic structure; thus inhibiting reactivity toward singlet oxygen produced during irradiation and improving the photostability. Therefore, the as‐prepared fluorinated GQDs with excellent photo‐ and pH stability are suitable for long‐term cellular imaging.
Caught on camera: By combining a microwave‐assisted technique with hydrothermal treatment and using fluorinated graphene oxide (FGO) as a raw material, fluorinated graphene quantum dots (GQDs) and nonfluorinated GQDs are synthesized (see figure). Fluorinated GQDs show improved pH and photostability compared with nonfluorinated GQDs due to fluorine. Fluorinated GQDs are suitable for long‐term cellular imaging.
Manipulation of cell-cell interactions has potential applications in basic research and cell-based therapy. Herein, using a combination of metabolic glycan labelling and bio-orthogonal click ...reaction, we engineer cell membranes with β-cyclodextrin and subsequently manipulate cell behaviours via photo-responsive host-guest recognition. With this methodology, we demonstrate reversible manipulation of cell assembly and disassembly. The method enables light-controllable reversible assembly of cell-cell adhesion, in contrast with previously reported irreversible effects, in which altered structure could not be reused. We also illustrate the utility of the method by designing a cell-based therapy. Peripheral blood mononuclear cells modified with aptamer are effectively redirected towards target cells, resulting in enhanced cell apoptosis. Our approach allows precise control of reversible cell-cell interactions and we expect that it will promote further developments of cell-based therapy.
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