ABSTRACT
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O2 and H2O2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co2+ and release CaO2 and graphene quantum dots (GQDs). The exposed CaO2 reacted with water to generate H2O2 and O2. The self-supplied O2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H2O2 was catalyzed by endogenous Co2+ to produce hydroxyl radicals for Co2+-triggered CDT. In vitro and in vivo experiments confirm that CaO2/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO2/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO2/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biocompatible Materials/pharmacology , Hydrogen Peroxide/pharmacology , Imidazoles/pharmacology , Oxygen/pharmacology , Photochemotherapy , Wound Infection/drug therapy , Zeolites/pharmacology , Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Escherichia coli/drug effects , Hydrogen Peroxide/chemistry , Hydrogen-Ion Concentration , Imidazoles/chemistry , Materials Testing , Microbial Sensitivity Tests , Molecular Structure , Nanoparticles/chemistry , Oxygen/chemistry , Particle Size , Reactive Oxygen Species/metabolism , Staphylococcus aureus/drug effects , Wound Infection/metabolism , Zeolites/chemistryABSTRACT
Common bacterial pathogens have become resistant to traditional antibiotics, representing an indispensable public health crisis. Photodynamic therapy (PDT), especially when common visible light sources are used as photodynamic power, is a promising bactericidal method. Based on the special photodynamic properties triggered by commonly available light emitting diode (LED) lamps, a kind of graphene quantum dots (GQDs) based composite system (termed GQDs@hMSN(EM)) was prepared through loading both GQDs and erythromycin (EM) into the hollow mesoporous silica nanoparticle (hMSN), aiming to achieve joint antimicrobial effect. Bacterial density experiments confirmed that GQDs@hMSN(EM) had combined antimicrobial effects from photodynamic effect and drug release on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In animal models, the healing degree of wounds infected by bacteria also confirmed that GQDs@hMSN(EM) group had the best therapeutic effect, with the significantly reduced inflammatory factors in blood. Different from traditional GQDs synthesized by solvothermal method, the as-prepared GQDs@hMSN can produce singlet oxygen (1O2) under light exposure to destroy the structure of bacteria, thus achieving highly efficient antimicrobial effect. The GQDs@hMSN(EM) in this work possesses good antimicrobial activity, sufficient drug loading, and controllable drug release ability, which provides a new opportunity for GQDs-based nanoplatform to enhance antimicrobial effect and reduce their drug resistance.
Subject(s)
Anti-Bacterial Agents/chemistry , Graphite/chemistry , Quantum Dots/chemistry , Animals , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/metabolism , Bacterial Infections/pathology , Disease Models, Animal , Drug Carriers/chemistry , Drug Liberation , Erythromycin/chemistry , Erythromycin/metabolism , Erythromycin/pharmacology , Erythromycin/therapeutic use , Escherichia coli/drug effects , Female , Light , Male , Mice , Nanoparticles/chemistry , Porosity , Quantum Dots/toxicity , Silicon Dioxide/chemistry , Singlet Oxygen/metabolism , Staphylococcus aureus/drug effects , Wound Healing/drug effectsABSTRACT
Due to excellent optical properties, CdTe quantum dots (QDs) exhibit great potential in cancer imaging. However, CdTe QDs can be quickly cleared out before reaching the desired location because of their ultra-small size. The structure and optical properties of CdTe QDs are also easily affected by the surrounding solution, which leads to their compromised applications in vivo. Here, CdTe QDs were incorporated into hollow mesoporous silica nanoparticles (hMSN) to form CdTe@hMSN nano-platforms. The as-synthesized system maintained the excellent emission properties of CdTe QDs; meanwhile, relatively high drug loading efficiency was also observed for doxorubicin (DOX). With the target for vascular endothelial growth factor (VEGF), the formed CdTe@hMSN(DOX)-VEGF Abs showed feasibility of tumor-oriented drug delivery and CdTe@hMSN conjugate accumulation. The high accumulation and enhanced targeted drug delivery of CdTe@hMSN conjugates in tumor nodules confirmed that CdTe@hMSN conjugates can serve as promising candidates for cancer detection and treatment.
