Enzyme-like biomimetic oral-agent enabling modulating gut microbiota and restoring redox homeostasis to treat inflammatory bowel disease.

Reactive oxygen species (ROS), immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease (IBD). Herein, a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed, using yeast cell wall (YCW) as the outer shell and zinc-doped Prussian blue analogue (ZnPBA) nanozyme inside. When orally administered, the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E. coli, meanwhile exhibiting improved intestinal epithelial barrier repair. Moreover, it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway. More importantly, the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity, significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E. coli to the same level as normal mice. Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

Effect of ROS generation on highly dispersed 4-layer O-Ti7O13 nanosheets toward tumor synergistic therapy.

Ultra-thin two-dimensional nanosheets have attracted increasing attention due to their great application prospects in nanomaterial science and biomedicine. Herein, we report the preparation of exfoliated raw and oxidized 4-layer Ti7O13 (O-Ti7O13) and their ability to produce reactive oxygen species (ROS). The results show that O-Ti7O13 nanosheets can effectively produce ROS induced by X-ray irradiation. The 4-layer nanosheets can quickly load doxorubicin (DOX) within 5 min with a high loading rate to obtain a novel nanodrug system through their electrostatic adsorption capacity, and they exhibit a sustained release behavior. In this way, chemotherapy, radiation therapy and photodynamic therapy effectively combine for cancer synergistic treatment. We evaluated the cytotoxicity, cellular uptake and intracellular location of the O-Ti7O13 nanosheet-based drug delivery system in A549 lung cancer cells. Our results show that the O-Ti7O13/DOX complex is more cytotoxic to A549 cells than free DOX since a low concentration of loaded DOX (10 µg/mL) with a low dose of X-rays can cause the complete apoptosis of tumor cells. This work reveals that the therapeutic effect of DOX-loaded O-Ti7O13 nanosheets is strongly dependent on their loading mode, and the effects of chemotherapy and photodynamic therapy are enhanced under X-ray irradiation, which allows O-Ti7O13 nanosheet use as a photo-activated drug carrier. This work provides a new strategy for preparing 2D metal oxide nanosheets toward biomedical applications.

Synthesis of surfactant-modified ZIF-8 with controllable microstructures and their drug loading and sustained release behaviour.

Metal-organic frameworks (MOFs) as drug carriers have many advantages than traditional drug carriers and have received extensive attention from researchers. However, how to regulate the microstructure of MOFs to improve the efficiency of drug delivery and sustained release behaviour is still a big problem for the clinical application. Herein, the authors synthesise surfactant-modified ZIF-8 nanoparticles with different microstructures by using different types of surfactants to modify ZIF-8. The surfactant-modified ZIF-8 nanoparticles have the larger specific surface area and total micropore volumes than the original ZIF-8, which enables doxorubicin (DOX) to be more effectively loaded on the drug carriers and achieve controlled drug sustained release. Excellent degradation performance of ZIF-8 nanoparticles facilitates the metabolism of drug carriers. The formulation was evaluated for cytotoxicity, cellular uptake and intracellular location in the A549 human non-small-cell lung cancer cell line. ZIF-8/DOX nano drugs exhibit higher cytotoxicity towards cells in comparison with free DOX, suggesting the potential application in nano drugs to cancer chemotherapy.

SiO2-coated magnetic nano-Fe3O4 photosensitizer for synergistic tumour-targeted chemo-photothermal therapy.

In this study, we integrated chemotherapy and photothermal therapy in a magnetically targeted doxorubicin-loaded Fe3O4@SiO2 nanodrug system. Size-controllable magnetic Fe3O4@SiO2 core-shell nanoparticles were synthesized via a solvothermal method and a modified Stǒber method. A molecular anticancer drug, namely, doxorubicin, was loaded onto Fe3O4@SiO2 nanocomposites to form a magnetically targeted drug delivery system. This drug delivery system exhibits pH-sensitive effects on drug loading and release. The drug loading rate in a neutral environment is higher than that in an acidic environment; the opposite property is observed for the release rate. In addition, the magnetic Fe3O4@SiO2 nanocomposites exhibit a satisfactory photothermal effect under NIR (808 nm) irradiation. The temperature can increase to 55 °C after only 10 min of irradiation, which effectively induces apoptosis of cancer cells in vitro. The cytotoxicity and cellular uptake of Fe3O4@SiO2@DOX nanodrugs were evaluated in A549 lung cancer cells. After treatment with Fe3O4@SiO2@DOX that contains only 10 µg/mL of DOX, 82.8% of A549 lung cancer cells can be killed. Furthermore, 81.3% of A549 lung cancer cells are killed after incubation with Fe3O4@SiO2@DOX that contains only 0.5 µg/mL of DOX and 15 min of NIR irradiation, thereby suggesting an excellent synergistic chemo-photothermal effect in tumour therapy. Our results suggest a new approach for the synthesis of a multifunctional, highly targeted, size-controlled nanodrug for tumour synergistic therapy.

Soft X-ray-Enhanced Reactive Oxygen Species Generation in Mesoporous Titanium Peroxide and the Application in Tumor Synergistic Therapy.

Mesoporous titanium peroxide TiOx nanospheres with a high surface area are synthesized for the application of an advanced drug system. The mesoporous TiOx nanospheres have a high specific surface area of 681.89 m2/g and suitable pore size (∼3 nm) that can effectively upload doxorubicin (DOX) and possesses a high drug storage capacity of 146.08%. They show a distinct ability to produce reactive oxygen species (ROS) in response to X-ray irradiation, which can effectively improve the radiotherapy in tumor treatment using the lung cancer cell line. The ROS generation of TiOx is more than ten-fold higher than that of TiO2. No apparent toxicity is found for the TiOx material itself without X-ray irradiation. In vitro and in vivo experiments show that TiOx/DOX nanodrugs significantly enhance cytotoxicity in response to X-ray irradiation. CCK8 assays display that the TiOx/DOX nanodrug has higher cancer treatment efficiency in response to X-ray irradiation because of the synergistic effect of chemotherapy and generation of ROS. In the in vivo experiments using lung cancer tumor-bearing mice model, the tumor inhibition rate in the TiOx/DOX + X-ray group increased by 90.4% compared to the untreated control group, showing a good synergistic chemo-radiotherapy effect in tumor treatment.

Dual-stimuli-responsive TiO x /DOX nanodrug system for lung cancer synergistic therapy.

Biological applications of nanosheets are rapidly increasing currently, which introduces new possibilities to improve the efficacy of cancer chemotherapy and radiotherapy. Herein, we designed and synthesized a novel nano-drug system, doxorubicin (DOX) loaded titanium peroxide (TiO x ) nanosheets, toward the synergistic treatment of lung cancer. The precursor of TiO2 nanosheets with high specific surface area was synthesized by a modified hydrothermal process using the polymer P123 as a soft template to control the shape. TiO x nanosheets were obtained by oxidizing TiO2 nanosheets with H2O2. The anti-cancer drug DOX was effectively loaded on the surface of TiO x nanosheets. Generation of reactive oxygen species, including H2O2, ·OH and ·O2 -, was promoted from TiO x nanosheets under X-ray irradiation, which is effective for cancer radiotherapy and drug release in cancer cells. In this way, chemotherapy and radiotherapy were combined effectively for the synergistic therapy of cancers. Our results reinforce the DOX loaded TiO x nanosheets as a pH sensitive and X-ray controlled dual-stimuli-responsive drug release system. The cytotoxicity, cellular uptake, and intracellular location of the formulations were evaluated in the A549 human non-small cell lung cancer cell line. Our results showed that TiO x /DOX complexes exhibited a greater cytotoxicity toward A549 cells than free DOX. This work demonstrates that the therapeutic efficacy of DOX-loaded TiO x nanosheets is strongly dependent on their loading mode and the chemotherapeutic and radiotherapy effect is improved under X-ray illumination, which provides a significant breakthrough for future applications of TiO x as a light activated drug carrier in cancer chemotherapy and radiotherapy.