Metal−organic frameworks (MOFs)-based peroxidase mimics have been seldom applied in the biomedical field, especially in vivo. One of the main reasons is their optimum reactions occur in strong acidic environments with a pH of 3−4, severely limiting their applications in living systems where neutral pH is usually required. Other types of peroxidase mimics also suffer such a fatal defect. Additionally, the direct introduction of the relatively high concentrated and toxic reaction reagent H 2 O 2 would induce undesired damage to normal tissues. Herein, a MOF-based hybrid nanocatalyst as a benign and self-activated cascade reagent has been constructed. Owing to better catalytic performance compared with threedimensional bulk MOF, an ultrathin two-dimensional (2D) MOF (2D Cu-TCPP(Fe)) nanosheet is chosen as a model of peroxidase mimic to physically adsorb glucose oxidase (GOx) for fabricating such a hybrid nanocatalyst. Nontoxic glucose can be continuously converted into abundant gluconic acid and H 2 O 2 by GOx, avoiding the direct use of relatively high concentrated and toxic H 2 O 2 and minimizing the harmful side effects. The generated gluconic acid can decrease the pH value from 7 to 3−4, dramatically activating the peroxidase-like activity of 2D Cu-TCPP(Fe) nanosheets. Meanwhile, the produced H 2 O 2 is used for subsequent catalysis of activated 2D Cu-TCPP(Fe) nanosheets, leading to efficient generation of an extremely toxic hydroxyl radial and antibacterial capacity. In vitro and in vivo results illustrate the designed benign and self-activated cascade reagent possesses a robust antibacterial effect with negligible biotoxicity.
Based on a series of biochemical experiments for analysis and characterization, it is found that the uncharged C-dots have no effect on bacterial growth while the negatively charged and positively charged C-dots can induce bacteria apoptosis. For the positively charged C-dots, they can induce both bacteria apoptosis and bacteria death. These observations will provide new insights into bioapplications of carbon dots.
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.
Recently, quorum sensing (QS) inhibitors (QSIs) have been combined with antibiotics to enhance antibiofilm efficacy in vitro and in vivo. However, targeting QS signals alone is not enough to prevent bacterial infections. Drug resistance and recurrence of biofilms makes it difficult to eradicate. Herein, photodynamic therapy (PDT) is selected to unite QSIs and antibiotics. A synergistically antibiofilm system, which combines QSIs, antibiotics, and PDT based on hollow carbon nitride spheres (HCNSs) is envisaged. First, HCNS provides the multidrug delivering ability, enabling QSIs and antibiotics to be released in sequence. Subsequently, multistage releases sensitize bacteria effectively, potentiating the chemotherapeutic effects of the antibiotics. Finally, the integration of QSIs and PDT not only minimizes the possibility of drug resistance, but also overcomes the problem of limited mass and extension of PDT. Even after 48 h of incubation, the bacterial biofilm is obviously inhibited. And its biofilm disperse efficiency exceeds 48% (compared with QSI‐potentiated chemotherapy group) and 40% (compared with PDT group). Besides, the inhibition of the QS system influences phenotypes related to virulence factor production and surface hydrophobicity, which weaken biofilm invasion and formation. Eventually, this system is applied to disperse bacterial biofilm in vivo. Overall, PDT and QS modulation are devoted to eradicate drug resistance and recurrence of the biofilm.
As a novel technique, photochemical internalization (PCI) has been employed as a new approach to overcome endo/lysosomal restriction, which is one of the main difficulties in both drug and gene delivery. However, the complicated synthesis procedure (usually requiring the self-assembly of polymers, photosensitizers and cargos) and payload specificity greatly limit its further application. In this paper, we employ a highly fluorescent graphitic hollow carbon nitride nanosphere (GHCNS) to simultaneously serve as a PCI photosensitizer, an imaging agent and a drug carrier. The surface modification of GHCNS with multifunctional polysaccharide hyaluronic acid (HA) endows the system with colloidal stability, biocompatibility and cancer cell targeting ability. After CD44 receptor-mediated endocytosis, the nanosystem is embedded in endo/lysosomal vesicles and HA could be specially degraded by hyaluronidase (Hyal), inducing open pores. In the following, with visible light illumination, GHCNS could produce ROS that effectively induced lipid peroxidation and caused endo/lysosomal membrane break, accelerating the cytoplasmic release of the drug in the targeted and irradiated cells. As a result, significantly increased therapeutic potency and specificity against cancer cells could be achieved.
The effective guidance of mesenchymal stem cell (MSC) differentiation on a substrate by near-infrared (NIR) light is particularly attractive for tissue engineering and regenerative medicine. However, most of current substrates cannot control multidirectional differentiation of MSCs like natural tissues. Herein, a photocontrolled upconversion-based substrate was designed and constructed for guiding multidirectional differentiation of MSCs. The substrate enables MSCs to maintain their stem-cell characteristics due to the anti-adhesive effect of 4-(hydroxymethyl)-3-nitrobenzoic acid modified poly(ethylene glycol) (P1) attached on the upconversion substrate. Upon NIR irradiation, the P1 is released from the substrate by photocleavage. The detachment of P1 can change cell-matrix interactions dynamically. Moreover, MSCs cultured on the upconversion substrate can be specifically induced to differentiate to adipocytes or osteoblasts by adjusting the NIR laser. Our work provides a new way of using NIR-based upconversion substrate to modulate the multidirectional differentiation of MSCs.
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