Collection of and Tumor Treatment(202512)
Bone implant-related infections are characterized by a high risk of delayed incidence or recurrence. Current antibacterial strategies often lack selectivity, leading to collateral damage to normal tissues and cells during bacterial eradication. To address this, mesoporous bioactive glass (MBG) was used as a base material in this study. By leveraging the near-infrared (NIR) photothermal response of S-NO bonds to release NO radicals and the antibacterial properties of Cu2+, MBG-RSNO powder was synthesized through amino-functionalized conjugation of S-nitrosothiols (RSNO) for nitric oxide free radicals (NO·) delivery, while PMBG@Cu powder was prepared via dopamine polymerization and Cu2+ chelation. These two powder materials were further processed through 3D printing to fabricate a PMBG@Cu/MBG-RSNO composite antibacterial scaffold. This scaffold demonstrated a strong NIR photothermal response, with pulsed 808 nm laser irradiation enabling the sustained release of NO· up to 113.71 μg per 100 mg of MBG-RSNO and increasing the temperature to approximately 40 ℃, facilitating efficient bacterial elimination. Antibacterial performance of the scaffold was evaluated using Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) as representative Gram-positive and Gram-negative bacteria, respectively, with and without external NIR stimulation. The results revealed that the PMBG@Cu/MBG-RSNO composite scaffold achieved an antibacterial efficiency of 99.9% against both bacterial strains. In summary, the PMBG@Cu/MBG-RSNO composite scaffold offers a promising solution to address infection challenges in bone implant materials and supports bone defect repair.
As a new type of photothermal compound, bismuth-based nanomaterials have advantages of low toxicity, environmental friendliness, and cheap raw materials, showing great application potential in biological photothermal therapy, but their photothermal conversion efficiency and antibacterial property are still low. In this study, based on the confined gelation method reported by previous literature, a silica-based hybrid micellar precursor with organosilica- stabilized micellar cores was prepared using Pluronic polymer F127 and 3-mercaptopropyl-trimethoxy-silane as raw materials, and a facile “confined reduction/sulfuration” method was further developed, that is, the abundant thiol groups in the organosilica framework of the micelle core were used as restricted adsorption sites, sodium borohydride was used as reducing agent, and sodium sulfide was used as vulcanizing agent to prepare ultra-small and amorphous bismuth sulfide clusters-supported silica-based hybrid micellar system. The results show that the functional hybrid micellar system has excellent photothermal performance, and its photothermal conversion efficiency is up to 86.93%, which may be attributed to monodisperse and stable loading of bismuth sulfide clusters with defective structure in the organosilica framework of hybrid micellar system, which enhances light absorption capacity of bismuth sulfide nanomaterials in the near-infrared wavelength range. The in vitro antimicrobial experiments show that this bismuth- containing system exhibits excellent photothermal antibacterial properties under irradiation of 808 nm near-infrared laser and good biocompatibility.
Nano-calcium phosphate (nCaP) has potential applications in nanomedicine fields such as drug delivery, bioimaging, antibacterial treatment, and bone formation promotion. However, its distribution and metabolic patterns within the body are not yet fully understood and require further in-depth research. This study employs a rare earth europium ion fluorescence labeling method and uses tumor-bearing mice as a model to investigate the distribution and metabolism of two sizes of nCaP (nanodots NDs: (2.53±0.63) nm; nanoparticles NPs: (107.76±25.37) nm×(17.66±1.63) nm) in the liver, spleen, lung, kidney, and tumor tissue. The results showed that after tail vein injection of 200 μL with a mass concentration of 1.5 mg/mL nCaP into tumor-bearing nude rats for 4 h, CaP NPs were primarily distributed in the liver and spleen, accounting for 65.70% and 29.32%, respectively, with 3.83% in the lung, while only 0.84% and 0.32% in the kidney and tumor. This suggests that larger CaP NPs are more easily captured by phagocytes within the reticuloendothelial system (RES). In contrast, compared to CaP NPs, accumulation of CaP NDs in the liver, spleen, and lung decreased significantly by 89.40%, 87.00%, and 88.89%, respectively, while their accumulation in the kidney and tumor increased by 3.67 and 3.06 times. This indicates that smaller particle size facilitates CaP NDs in glomerular filtration for urinary excretion and enhances their tumor-targeting capability. The clearance rates (CLz) of CaP NDs in the liver, spleen, and lung were 6.60, 4.14, and 2.40 times higher than that of CaP NPs, respectively, and 42.29% in the kidney. This indicates that reduced size of CaP NDs facilitates rapid metabolism by phagocytes in the liver, spleen, and lung but also results in reabsorption in the renal tubules. In tumor, the CLz of CaP NDs decreased by 91.9%, much smaller than that of CaP NPs, suggesting that the smaller CaP NDs exhibit significantly enhanced tumor targeting and retention capability. In the meantime, a physiologically based pharmacokinetic (PBPK) model incorporating particle size factors was preliminarily established for tumor-bearing mice to simulate the distribution of nano-calcium phosphate. The model's predictive fit (R2) for CaP NDs and CaP NPs in tumor sites reached 0.925 and 0.827, respectively. This study provides promising support for understanding in vivo distribution and metabolic patterns of nCaP and applying potential in medicine.
Inorganic non-metallic biomaterial is one of main types of biomaterials, which is widely used in biomedical fields such as tissue repair, tumor therapy, and drug delivery., making an important contribution to national life and health. Research on inorganic non-metallic biomaterials in China is flourishing, but their production and application are still in the stage of overcoming difficulties. To realize the high-quality development of China's inorganic non-metallic biomaterials and improve their hard power to protect national life and health, this paper analyzes hotspots and difficult problems in research and application of China's inorganic non-metallic biomaterials by means of strategic study. Based on current development opportunities and challenges, some suggestions are proposed for the development of inorganic non-metallic biomaterials, such as material design for unique performance, research on materiobiology, exploration of new principles and mechanisms mediated by materials, customization by intelligent personalization, design through big data screening and artificial intelligence, and standardization based evaluation/regulation. This aims to provide guidance for development of inorganic non-metallic biomedical products and push forward scientific research while accumulating talent resources.
Dental resins are currently the most commonly used filling materials for dental caries clinically due to their advantages of aesthetics, safety, and easy operation. However, their service life is limited because of their low mechanical strength and insufficient antibacterial activity. In this study, radial mesoporous silica was prepared firstly, and then loaded nanosilver into its porous channels to obtain silver loaded radial mesoporous silica (Ag-RMS). Effects of different contents of Ag-RMS on antibacterial, mechanical, and physicochemical properties of dental composite resins were studied. The results showed that Ag-RMS could significantly improve the antibacterial performance of composite resins, achieving an antibacterial rate of 99.68% against Streptococcus mutans when the addition amount of Ag-RMS was 5% (mass fraction). Mechanical strength of the composite resin gradually increased with the increase of Ag-RMS content. When the addition amount of Ag-RMS reached 7% (in mass), the flexural strength of composite resins was 28.16% higher than that of resin matrix. Moreover, the addition of Ag-RMS had almost no obvious effect on their polymerization shrinkage rate, monomer conversion rate, curing depth, and surface hydrophobicity. These results indicate that the prepared Ag-RMS in this study can improve the comprehensive performance of the novel composite resins.
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.
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.
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.
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.
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.