Collection of Anti-bacteria and Tumor Treatment(202412)

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Novel Magnetoelectric Catalytic Nanoparticles: RNS Release and Antibacterial Efficiency
ZHANG Zhimin, GE Min, LIN Han, SHI Jianlin
Journal of Inorganic Materials    2024, 39 (10): 1114-1124.   DOI: 10.15541/jim20240152
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Compared with antibiotics and other drugs with poor functionalities and risk to induce bacterial resistance, inorganic functional nanomaterials with catalytic activity occupy an increasingly important position in the treatment of pathogenic infections by advantages of high response to the infected microenvironment (e.g. weak acid, high H2O2 concentration) or external physical stimuli (e.g. laser, ultrasound) and broad-spectrum sterilization. However, the acidic infection microenvironment is weak and unstable, and light or sound signals with high power density will cause damage to human cells. In addition, antimicrobial applications of alternative magnetic field (AMF), a non-invasive signal type with high tissue penetration, convenience to be remotely controlled, and effective magnetoelectric catalysis based on AMF have not been reported. In this study, an AMF-responsive nanocatalytic strategy based on the magnetostrictive-piezoelectric catalytic effect was applied to antibacterial research, and the surface of CoFe2O4-BiFeO3 magnetoelectric nanoparticles (BCFO) was modified with the nitrogen-containing group L-arginine (LA) to achieve a magneto-electric responsive controlled release of powerful bactericide reactive nitrogen species (RNS). In AMF, BCFO simultaneously generates reactive oxygen species (ROS) hydroxyl radical (·OH) and superoxide anion (·O2-). The former reacts with LA to release nitric oxide (NO), and the latter combines with NO to produce peroxynitrite (ONOO-), a typical RNS. As a highly active nitrification and oxidation agent, ONOO- could exhibit stronger antibacterial activity than ROS under biofriendly AMF. Successful production of ONOO- and achievement of stronger bactericidal efficiency were validated in this study. This work not only applies magnetoelectric nanocatalysis for antibacterial purposes, but also significantly improves the antibacterial ability through the conversion of ROS to RNS.

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Sonodynamic and Enzyme-like Activities of Niobium-based Coatings: Antimicrobial, Cell Proliferation and Cell Differentiation
ZHANG Shumin, XI Xiaowen, SUN Lei, SUN Ping, WANG Deqiang, WEI Jie
Journal of Inorganic Materials    2024, 39 (10): 1125-1134.   DOI: 10.15541/jim20240160
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Currently, repair of infectious bone defects is still a clinical serious challenge. Here, a heterojunction coating of niobium oxide on pure niobium surface by using microarc oxidation and hydrothermal treatment was prepared. The results showed that the obtained heterogeneous junctions exhibited synchronously enzyme-like and ultrasonic dynamic properties triggered by ultrasound treatment, especially in acidic microenvironment of mimic bacterial infection. Under these key conditions, oxidase-like activity of the heterogeneous junctions was enhanced, generating several reactive oxygen species which can kill bacteria and remove their biofilm, with inhibition and clearance rates were 98.57% and 91.43%, respectively. Under simulated physiological conditions, ultrasound enhanced antioxidant-like enzyme activity of this kind heterogeneous junction, thereby scavenging reactive oxygen species, alleviating oxidative stress, and promoting proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (rBMSCs). In conclusion, the obtained niobium-based coatings with sonodynamic and enzyme-like activities have profound potential application prospects in infectious bone repair.

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Anti-metastatic Immunotherapy of Advanced Tumors Based on EDTA Intercalated Zinc-aluminum Layered Double Hydroxide
LI Shiqi, BAO Qunqun, HU Ping, SHI Jianlin
Journal of Inorganic Materials    2024, 39 (9): 1044-1052.   DOI: 10.15541/jim20240154
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Systemic metastasis of cancer cells is currently the main cause of death for patients with advanced cancer. Due to the rapid proliferation of tumor cells and abnormal deposition of extracellular matrix, the large-volume tumor tissue in advanced cancer is dense and stiff, which brings great difficulties to the treatment of advanced solid tumors: conventional drugs having difficulty in penetrating and immune cells facing challenges to infiltrate into their interior. Meanwhile, tumor cells on hard matrices have stronger invasive ability, which is prone to cause systemic metastasis of tumors. To solve this problem, this study prepared ethylenediaminetetraacetic acid (EDTA) intercalated zinc-aluminum layered double hydroxide nanomaterials (EDTA/LDH). Based on two parallel Ca2+ deprivation mechanism, the anti-metastasis immunotherapy of EDTA/LDH material system for advanced large-volume solid tumors was studied. In the slightly acidic tumor microenvironment, the material system adheres to the tumor cell membrane through electrostatic force, releases EDTA to chelate Ca2+ in cell adhesion proteins, cuts off part of the cell connections, reduces the stiffness of large tumors, and promotes the infiltration of immune cells into the tumor tissue. In addition, the material system is phagocytosed by macrophages as a "foreign body", causing calcium store-operated calcium influx, activating the anti-tumor immune effect of macrophages, and inhibiting the tumor-promoting invasion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and regulatory T cells (Tregs). This study will provide reference ideas and methods for the anti-metastasis treatment of advanced malignant solid tumors.

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Fe3O4-DMSA-PEI Magnetic Nanoparticles with Small Particle Size: Preparation and Gene Loading
CAI Heqing, HAN Lu, YANG Songsong, XUE Xinyu, ZHANG Kou, SUN Zhicheng, LIU Ruping, HU Kun, WEI Yan
Journal of Inorganic Materials    2024, 39 (5): 517-524.   DOI: 10.15541/jim20230464
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Ferroferric oxide (Fe3O4) magnetic nanoparticles are widely used as passive targeting carriers in gene therapy, due to their simple preparation, targeting under external magnetic field and easy surface grafting. This study synthesized oil phase Fe3O4 nanoparticles with controllable particle sizes in the range from 4 to 9 nm by regulating the accumulation growth time in the solvothermal method. Then, meso-2, 3-dimercaptosuccinic (DMSA) was employed to double exchange oleic acid molecules on its surface to provide good water dispersibility. Finally, Fe3O4-DMSA-PEI magnetic nanoparticles were obtained by grafting branched polyethylenimine (PEI) onto Fe3O4-DMSA surface through amidization reaction. The results demonstrate that the Fe3O4-DMSA-PEI magnetic nanoparticles have a surface Zeta potential of (52.50 ± 1.94) mV, remaining a certain degree of superparamagnetism (14.48 emu/g, 1 emu/g=1 A∙m2/kg). When the mass ratio of Fe3O4-DMSA-PEI magnetic nanoparticles to plasmid DNA is 15 : 1, it can completely block DNA and its loading capacity is as high as 6.67%. The Fe3O4-DMSA-PEI magnetic nanoparticles prepared in this study have a certain gene delivery ability and are expected to be used as gene carriers in the field of gene transfection.

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pH Responsive Copper-Doped Mesoporous Silica Nanocatalyst for Enhanced Chemo-Chemodynamic Tumor Therapy
HE Qian, TANG Wanlan, HAN Bingkun, WEI Jiayuan, LÜ Wenxuan, TANG Zhaomin
Journal of Inorganic Materials    2024, 39 (1): 90-98.   DOI: 10.15541/jim20230151
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Chemodynamic therapy (CDT) uses endogenous H2O2 of tumor cells to react with Fenton catalysts to generate highly toxic hydroxyl radical (•OH), thereby killing cancer cells. However, the insufficient endogenous H2O2 and low transport efficiency of nanoparticles result in unsatisfactory anticancer efficacy. Here, we successfully synthesized a Cu2+ doped mesoporous silica nanoparticles (Cu-MSN) with excellent dispersity and small size. After loaded with doxorubicin (DOX) and ascorbate (AA), Cu-MSN was coated with folic acid (FA), dimethyl maleic anhydride (DMMA) modified chitosan (FA-CS-DMMA) and carboxymethyl chitosan (CMC) to obtain a pH responsive targeted nanocatalyst FCDC@Cu-MSN@DA. SEM images showed that particle size of FCDC@Cu-MSN@DA was about 100 nm. After 48 h in vitro, cumulative amount of Cu2+ release reached 80% and DOX release was about 57.3% in the acidic environment. After oxidation of AA, the produced exogenous H2O2 induced Cu2+ to catalytic the Fenton-like reaction, which enhanced the therapeutic effect of tumor chemodynamic therapy (CDT). Cell experiments in vitro demonstrated that FCDC@Cu-MSN@DA exhibited excellent anticancer ability in the combination of CDT and chemotherapy. This multifunctional nanocatalyst has great potential application in cancer therapy in the future.

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Copper-based Nanozymes: Properties and Applications in Biomedicine
NIU Jiaxue, SUN Si, LIU Pengfei, ZHANG Xiaodong, MU Xiaoyu
Journal of Inorganic Materials    2023, 38 (5): 489-502.   DOI: 10.15541/jim20220716
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Natural enzymes play an important role in maintaining normal life activities, but suffer in their inherent instability, harsh reaction conditions and high purification costs, which limit their wide applications in vitro. Compared to natural enzymes, nanozymes with high stability, low cost, and ease of structural regulation and modification attract the great interests and are widely applied to biomedicine, environmental control, industrial production and other fields due to their enzyme-like activities and selectivity. As an essential element and one of the active central metals of natural enzymes in the human body, copper-based (Cu-based) nanozymes have received extensive attentions and researches. This review focused on the classification of Cu-based nanozymes, such as Cu nanozymes, Cu oxide nanozymes, Cu telluride nanozymes, Cu single-atom nanozymes, and Cu-based metal organic framework nanozymes. Then this review described the enzyme-like activities and catalytic mechanisms of Cu-based nanozymes, and also summarized the applications of Cu-based nanozymes, including biosensing, wound healing, acute kidney injury, and tumors. The challenges and future development direction of Cu-based nanozymes were proposed.

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Construction of Prussian Blue Fluorescent Nanoprobe for Specific Detection of HClO in Cancer Cells
DU Qiujing, LIU Tianzhi, CHEN Jufeng, CHEN Hangrong
Journal of Inorganic Materials    2023, 38 (1): 55-61.   DOI: 10.15541/jim20220119
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Hypochlorous acid (HClO) is one of the reactive oxygen species (ROS), taking crucial parts in many physiological and pathological processes. However, excessive HClO causes tissue injuries, atherosclerosis, neurodegeneration diseases, and even cancers. Therefore, real-time detection of HClO in cancer cells is of importance for exploring the effect of HClO in tumor progression or immunotherapy. Quite different from present organic molecular probes, a novel inorganic-based hydrophilic fluorescent nanoprobe was developed by simply integrating fluorescein isothiocyanate (FITC) into hollow mesoporous Prussian Blue nanoparticles (HMPB) in this work. Owing to inner filter effect, fluorescence of FITC within HMPB quenches to some extent, which can be restored via the Fe2+-ClO- redox reaction. A typical fluorescence increase of FITC at emission peak of 520 nm can be clearly observed in the presence of HClO in vitro, which exhibits a good linear relationship in the range of 5×10-6-50×10-6 mol/L in HClO detection and its detection limit is calculated to be 2.01×10-6 mol/L. Furthermore, the cellular experiment demonstrates the specific detection capability of HClO in cancer cells with high sensitivity by the obtained nanoprobe.

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