Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC. RESULTS: Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast. CONCLUSIONS: The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

Applying a resting operation to alleviate bioclogging in vertical flow constructed wetlands: an experimental lab evaluation.

The aim of this study is to evaluate the effects of and analyze the reasons for applying a resting operation to alleviate bioclogging in vertical flow constructed wetlands (VFCWs). In parallel, three groups of laboratory-scale VFCWs were continuously fed with prepared wastewater (BOD = 600 mg/L) at a relatively high hydraulic loading rate of 0.5 m(3)/m(2)·d until clogging. Parameters related to the clogging of the wetland substrate before and after resting were examined and measured. The results showed that the resting operation could effectively alleviate bioclogging because the hydraulic conductivity and effective porosity were improved after 3, 7 and 10 days of resting. In the upper 0-10 cm layer, the hydraulic conductivity increased 2.0, 2.6 and 3.5 times, respectively, for the three resting periods. The reduction of the extracellular polymeric substance (EPS), biofilm decay and the consequential change in the biofilm structure are the main reasons that the resting operation relieved clogging. In addition, the observed and theoretical resting times (approximately 7 days) agreed well. The results provide a theoretical basis and technical support for solving clogging problems.

DNA-Functionalized Liposomes In Vivo Fusion for NIR-II/MRI Guided Pretargeted Ferroptosis Therapy of Metastatic Breast Cancer.

In clinic, metastasis is still the main reason for death for cancer patients. Therefore, it is necessary to track cancer metastases accurately, kill cancer cells effectively, and then improve the prognosis of patients with advanced cancer. Therefore, we designed a liposome-based pretargeted system modified with single-stranded DNA and targeting peptide injected in sequence and then assembled in vivo for multimodality imaging-guided pretargeted synergistic therapy of metastatic breast cancer. The pretargeted system is composed of the first liposome, loaded with near-infrared fluorescence imaging (NIR-II) probe downconversion nanoprobes (DCNP) and magnetic resonance imaging (MRI) contrast agent SPIO (L1/C-Lipo/DS), for primary/metastatic tumor MRI/NIR-II dual-modal imaging, and the second liposome, loaded with glucose oxidase (GOx) and doxorubicin (DOX) (L2/C-Lipo/GD), as the therapeutic component. The SPIO in L1/C-Lipo/DS accumulated in the tumor tissue will provide a necessary iron ion for the therapeutic liposome (L2/C-Lipo/GD) to exert the pretargeted ferroptosis therapy to cancer cells. We demonstrate that the DNA-mediated pretargeting strategy can realize the multimodality imaging-guided synergistically enhanced antitumor effect between the two liposomes. This pretargeted and synergistic in vivo assembly nanomedicine strategy for diagnosis and treatment holds clinical translation potential for cancer management.

Multifunctional Microspheres Dual-Loaded with Doxorubicin and Sodium Bicarbonate Nanoparticles to Introduce Synergistic Trimodal Interventional Therapy.

Lactic acid in the tumor microenvironment is highly correlated with the prognosis of tumor chemoembolization, but there are limited clinical strategies to deal with it. To improve the efficacy, NaHCO3 nanoparticles are innovatively introduced into drug-loaded microspheres to neutralize lactic acid in the tumor microenvironment. Here we showed that multifunctional ethyl cellulose microspheres dual-loaded with doxorubicin (DOX) and NaHCO3 nanoparticles (DOX/NaHCO3-MS) presented excellent antitumor effects by improving the pH of the tumor microenvironment. The homeostasis of the tumor microenvironment was continuously disturbed due to the sustained release of NaHCO3 nanoparticles, which also led to a significant increase in tumor cell apoptosis (compared with the control and DOX-MS groups). We also showed that the administration of DOX/NaHCO3-MS via the hepatic artery in a rabbit model of VX2 orthotopic liver cancer resulted in optimal antitumor efficacy, and the area of tumor necrosis at the embolization site was significantly increased and the proliferation of tumor cells was significantly weakened. The designed DOX/NaHCO3-MS exhibited strong synergistic antitumor effects of embolization, chemotherapy, and tumor microenvironment improvement. The present microspheres provided a strategy for the enhancement of the chemoembolization of hepatocellular carcinoma, which could also be extended to other clinical embolization treatments for blood-rich solid tumors.

Delivery strategies of cancer immunotherapy: recent advances and future perspectives.

Immunotherapy has become an emerging strategy for the treatment of cancer. Immunotherapeutic drugs have been increasing for clinical treatment. Despite significant advances in immunotherapy, the clinical application of immunotherapy for cancer patients has some challenges associated with safety and efficacy, including autoimmune reactions, cytokine release syndrome, and vascular leak syndrome. Novel strategies, particularly improved delivery strategies, including nanoparticles, scaffolds, and hydrogels, are able to effectively target tumors and/or immune cells of interest, increase the accumulation of immunotherapies within the lesion, and reduce off-target effects. Here, we briefly describe five major types of cancer immunotherapy, including their clinical status, strengths, and weaknesses. Then, we introduce novel delivery strategies, such as nanoparticle-based delivery of immunotherapy, implantable scaffolds, injectable biomaterials for immunotherapy, and matrix-binding molecular conjugates, which can improve the efficacy and safety of immunotherapies. Also, the limitations of novel delivery strategies and challenges of clinical translation are discussed.

Synthesis and in vitro degradation of a novel magnesium oxychloride cement.

Magnesium oxychloride cement (MOC) has been used in civil engineering as it exhibits a relatively high early strength and a low coefficient of thermal expansion. Its poor water resistance, although, has prevented its widespread use. Steady degradation when immersed in an aqueous environment, however, could be a beneficial property for a resorbable bone replacement. In this study, we have evaluated how different concentrations of phosphoric acid may be used to enhance water resistance providing some control over the rate of degradation. The phase compositions, microstructures, mechanical properties, and the degradation of MOC have been evaluated. As a preliminary assessment of biological suitability, the response of a population of bone marrow stromal cells to the surface was evaluated. X-ray diffraction data demonstrate that 5Mg(OH)2 ·MgCl2·8H2O (phase 5) was formed in all MOC samples. The MOC modified with H3PO4 exhibits good water resistance and can sustain strength in aqueous medium and by adjusting H3 PO4 concentration; degradation speed may be controlled. Cells cultured on the surface of the MOC attached and retained viability over the duration of the study.

Synthesis of bioactive ceramic on the titanium substrate by micro-arc oxidation.

Bioactive ceramic films on titanium substrate are prepared successfully by micro-arc oxidation in electrolyte solution containing NaOH only. The coatings are prepared by micro-arc oxidation at various applied current densities (200-400 mA/cm2) and in NaOH electrolyte with different concentrations. The XRD shows that they are composed of rutile, anatase, Na2Ti6O13, and Na2Ti4O9 phases. The composition and surface morphologies are strongly dependent on the applied current density and electrolyte concentration. For example, at high current density, the phase is mainly composed of rutile and Na2Ti6O13, and at high electrolyte concentration, it is Na2Ti6O13 phase. The morphologies of the samples vary with the increase of current and electrolyte concentration. The apatite-inducing ability of bioactive ceramic films is evaluated in biological model fluids. After soaking in biological model fluids, the titania-based coatings containing Na2Ti6O13 phase have excellent capability of inducing bone-like apatite.

Direct preparation of CaTi4 (PO4)6 coatings on the surface of titanium substrate by micro arc oxidation.

CaTi(4) (PO(4))(6) coatings was prepared on the surface of CP (commercially pure) Titanium substrate via micro arc oxidation in a newly designed electrolyte system. The preparation method -micro arc oxidation, as well as its discharge characterization was described and studied. The phases, morphology, chemical composition of the coatings were characterized by XRD, EDX and SEM analysis respectively. The results show: the main phase of the prepared coating was CaTi(4) (PO(4))(6) which is a bioactive coating material, the morphology of the coating was rather coarse and not like that of traditional MAO coating which was full of pores. Also the samples prepared in different electrolyte systems were studied and compared.