Radiotherapy combined with nano-biomaterials for cancer radio-immunotherapy.

Radiotherapy (RT) plays an important role in tumor therapy due to its noninvasiveness and wide adaptation. In recent years, radiation therapy has been discovered to induce an anti-tumor immune response, which arouses widespread concern among scientists and clinicians. In this review, we highlight recent advances in the applications of nano-biomaterials for radiotherapy-activated immunotherapy. We first discuss the combination of different radiosensitizing nano-biomaterials and immune checkpoint inhibitors to enhance tumor immune response and improve radiotherapy efficacy. Subsequently, various nano-biomaterials-enabled tumor oxygenation strategies are introduced to alleviate the hypoxic tumor environment and amplify the immunomodulatory effect. With the aid of nano-vaccines and adjuvants, radiotherapy refreshes the host's immune system. Additionally, ionizing radiation responsive nano-biomaterials raise innate immunity-mediated anti-tumor immunity. At last, we summarize the rapid development of immune modulatable nano-biomaterials and discuss the key challenge in the development of nano-biomaterials for tumor radio-immunotherapy. Understanding the nano-biomaterials-assisted radio-immunotherapy will maximize the benefits of clinical radiotherapy and immunotherapy and facilitate the development of new combinational therapy modality.

The Role of Decorin in the Adhesion Process of Treponema Pallidum Subspecies Pallidum to Human Brain Microvascular Endothelial Cells.

Objective: This study aims to investigate the role of decorin in the adhesion process of Treponema pallidum subspecies pallidum (T. pallidum) to human brain microvascular endothelial cells. Methods: The study involved an in vitro experimental design. Western blot analysis was conducted to determine the protein expression level of decorin in the cells. The cells were divided into four groups: Tp group, inactivated Tp group, LPS group, and negative control group. The adhesion of T. pallidum to the cells was analyzed using darkfield microscopy counting and quantitative polymerase chain reaction (qPCR). The cells were divided into four groups based on different preprocessing treatments: control group, decorin group, DCN-siRNA group, and DCN-siRNA+decorin group. Changes in the F-actin of the cells were explored using confocal laser scanning microscopy. The cells were divided into the Tp group, Tp+decorin group, and control group. Results: Western blot analysis showed high expression of decorin in the Tp group and LPS group. Darkfield microscopy counting revealed a significantly higher number of T. pallidum adhered to a single cell in the decorin group compared to the control group. Conversely, the number of adhered T. pallidum was significantly lower in the DCN-siRNA group compared to the control group. qPCR results indicated a considerably higher T. pallidum load in the decorin group compared to the control group. In the Tp group, T. pallidum treatment induced the reorganization of F-actin, while the distribution of F-actin in the Tp+decorin group was comparable to that of the control group. Conclusions: Decorin enhances the adhesion of T. pallidum to human brain microvascular endothelial cells, suggesting that decorin may act as one of the receptors regulating the adhesion of T. pallidum to cells. Furthermore, T. pallidum treatment triggers the rearrangement of F-actin in cells, and decorin plays a protective role in this process.

Direct evidence of visible surface plasmon excitation in ITO film coated on LiNbO3 slabs.

An iron-doped Y-cut lithium niobate (Fe:LN) slab was coated with indium-tin-oxide (ITO) thin films by magnetron sputtering. The electron confinement in a sub-nanometer region at ITO/LN interfaces is resulted from electric screening effect. Consequently, the local plasma frequency in the sub-nanometer metallic-like layer is shifted to the UV regime. This makes it possible to excite surface plasmon polaritons (SPPs) in the visible region with photorefractive phase gratings in the LN slab and to transport SPPs much energy-efficiently. Direct evidence of the excitation of SPPs was demonstrated by the presence of deep transmission spectral valleys in the transmission spectra and striking dark bands in the 2D diffraction patterns while using a white reading beam. Theoretical arguments and confirmation experiments are presented to elucidate all the related findings.

Ultralow loss visible surface plasmon based waveguides formed in indium-tin-oxide coated Fe-doped LiNbO3 slabs.

Visible reconfigurable waveguides were evidenced in a composite system formed with indium-tin-oxide (ITO) films coated on iron-doped lithium noibate (LN) slabs. Surface plasmon polaritions (SPPs) excited at the ITO/LN interface were believed to be behind the observed light guiding, which is inherent with superlow loss for its sub-nanometer modified layer. The forward near-surface-normal scattering and accompanying reduction of the specular reflectivity in the front ITO/LN interface are consistent with SPP excitation.

Impact of surface plasmon polaritons on photorefractive effect in dye doped liquid crystal cells with ZnSe interlayers.

Great impact of surface plasmon polaritons (SPPs) on photorefractive effect in ZnSe/liquid crystal interface was observed and studied in dye pyrromethane 597 doped 4,4'-n-pentylcyanobiphenyl (5CB) liquid crystal (LC) cells sandwiched with ZnSe coated ITO glass plates. Locally electrostatic modification of ZnSe in charge carrier density makes possible visible light excitation of SPPs in the LC/ZnSe interfaces. A tentative physical picture of SPP mediation was proposed in elucidating associated findings, including photoinduced scattering enhancement at low electric field and then reduction at high field, stepwise up- and down-turns in exponential gain coefficient, and 2D diffraction patterns. This work may open a new way toward tunable low-loss visible excitation of SPPs for plasmonic applications, specifically for organic plasmonics.

Impact of thickness of liquid crystal layer on response rate and exponential gain coefficient with assistance of ZnSe film.

A response time as short as 5.4 ms and an exponential gain coefficient as large as 1795.0 cm(-1) were obtained in C(60) doped 4,4'-n-pentylcyanobiphenyl liquid crystal cells sandwiched with two indium tin oxide glass plates coated with nanoscale photoconductive ZnSe films, which is believed to be facilitating charge-carrier generation and transportation and, hence, to be responsible for the fast response rate. The surface-mediated photorefractive effect and the ZnSe interlayers were both behind the high gain coefficients. The two-dimensional diffraction patterns observed in our system are also discussed.

Cause and consequence of heterogeneity in human mesenchymal stem cells: Challenges in clinical application.

Human mesenchymal stem cells (hMSCs) are mesoderm-derived adult stem cells with self-proliferation capacity, pluripotent differentiation potency, and excellent histocompatibility. These advantages make hMSCs a promising tool in clinical application. However, the majority of clinical trials using hMSC therapy for diverse human diseases do not achieve expectations, despite the prospective pre-clinical outcomes in animal models. This is partly attributable to the intrinsic heterogeneity of hMSCs. In this review, the cause of heterogeneity in hMSCs is systematically discussed at multiple levels, including isolation methods, cultural conditions, donor-to-donor variation, tissue sources, intra-tissue subpopulations, etc. Additionally, the effect of hMSCs heterogeneity on the contrary role in tumor progression and immunomodulation is also discussed. The attempts to understand the cellular heterogeneity of hMSCs and its consequences are important in supporting and improving therapeutic strategies for hMSCs.

Oxygen-Vacancy-Rich Monolayer BiO2- X Nanosheets for Bacterial Sepsis Management via Dual Physically Antibacterial and Chemically Anti-inflammatory Functions.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Effective treatment of bacterial sepsis remains challenging due to the rapid progression of infection and the systemic inflammatory response. In this study, monolayer BiO2- X nanosheets (BiO2- X NSs) with oxygen-rich vacancies through sonication-assisted liquid-phase exfoliation are successfully synthesized. Herein, the BiO2- X NSs exhibit a novel nanozyme-enabled intervention strategy for the management of bacterial sepsis, based on its pH dependent dual antibacterial and anti-inflammatory functions. BiO2- X NSs exhibit effective antibacterial by utilizing oxidase (OXD)-like activity. Additionally, BiO2- X NSs can scavenge multiple reactive oxygen species (ROS) and mitigate systemic hyperinflammation by mimicking superoxide dismutase (SOD) and catalase (CAT). These dual capabilities of BiO2- X NSs allow them to address bacterial infection, proinflammatory cytokines secretion and ROS burst collaboratively, effectively reversing the progression of bacterial sepsis. In vivo experiments have demonstrated that BiO2- X NSs significantly reduce bacterial burden, attenuate systemic hyperinflammation, and rapidly rescued organ damage. Importantly, no obvious adverse effects are observed at the administered dose of BiO2- X NSs. This study presents a novel defect engineering strategy for the rational design of high-performance nanozymes and development of new nanomedicines for managing bacterial sepsis.

A Prussian blue analog as a decorporation agent for the simultaneous removal of cesium and reactive oxygen species.

Radioactive cesium (Cs) is a significant concern due to its role as a major byproduct of nuclear fission and its potential for radioactive contamination. Internal contamination with radioactive Cs is characterized by immoderate production of reactive oxygen species (ROS), resulting in severe radiation damage. Therefore, the development of therapeutic strategies should focus on enhancing the excretion of radioactive Cs and reducing radiation-induced oxidative damage. However, current therapeutic drugs like Prussian blue (PB) have limited efficacy in addressing these issues. In this study, we present Cu3[Fe(CN)6]2 (CuFe) nanoparticles, a Prussian blue analog (PBA), which can not only efficiently sequester Cs but also exhibit resistance against radiation damage. The results of the adsorption studies demonstrate that CuFe outperforms PB in terms of adsorption performance. Further mechanistic investigations indicate that the increased adsorption capacity of CuFe may be attributed to the presence of additional defects resulting from the [Fe(CN)6] missing linkers. Moreover, CuFe mimics the functions of catalase (CAT) and superoxide dismutase (SOD) by effectively eliminating O2˙- and H2O2 while scavenging ˙OH, thereby mitigating ROS induced by radiative Cs. Importantly, in vivo study confirms the efficient Cs decorporation capability of CuFe. The fecal cumulative excretion rate of CuFe reaches 69.5%, which is 1.45 times higher than that of PB (48.8%). These findings demonstrate that CuFe exhibits excellent Cs removal performance and ROS scavenging ability, making it an attractive candidate for the treatment of Cs contamination.

Ultrasmall calcium-enriched Prussian blue nanozymes promote chronic wound healing by remodeling the wound microenvironment.

Chronic wound healing remains challenging due to the oxidative microenvironment. Prussian blue (PB) nanoparticles exhibiting multiple antioxidant enzyme-like activities have attracted widespread attention, while their antioxidant efficacy remains unsatisfied. Herein, ultrasmall calcium-enriched Prussian blue nanoparticles (CaPB NPs) are simply constructed with high yields for the wound repair application. Owing to the ultrasmall size and synergistic effect of the generated dual active sites, the CaPB NPs exhibit prominent antioxidase-like activities, protecting cells from oxidative stress-induced damage. In addition to the effect of Ca on regulating keratinocyte and fibroblast growth, it has been demonstrated that the administration of CaPB NPs obviously promoted wound closure as well as collagen deposition and neovascularization in the full-thickness wound defect model in mice. Importantly, the CaPB NP treatment can effectively up-regulate the expression levels of anti-inflammatory cytokines and vascular endothelial growth factors to remodel the wound microenvironment, thereby accelerating the wound healing process. Overall, this work reveals that metal atom substitution is an effective strategy to construct ultrasmall and high-catalytic-performance PB-based nanozymes and further potentiate their effectiveness for chronic wound management.

pH-Responsive epitope-imprinted magnetic nanoparticles for selective separation and extraction of chlorogenic acid and caffeic acid in traditional Chinese medicines.

Chlorogenic acid and caffeic acid often coexist in traditional Chinese medicines (TCMs) and play roles as antioxidation, antiviral, antitumor and anti-inflammatory agents. Due to their low content and the presence of structural analogues, they cannot be effectively separated by conventional extraction methods. Molecularly imprinted polymers, as synthesized receptors with antibody-like binding properties, have significant advantages in separating structural analogues. However, the harsh imprinting conditions easily induced the degradation of chlorogenic acid. Therefore, caffeic acid was used as an epitope template to replace chlorogenic acid for imprinting. Boronic acid-functionalized magnetic nanoparticles (MNPs) were selected as substrates, which could not only facilitate the immobilization and removal of the templates by pH regulation, but also achieve rapid separation under an external magnetic field. Tetraethyl orthosilicate was selected as an imprinting monomer which allowed for precise control of the thickness of the imprinting layer by adjusting the imprinting time. The prepared epitope-imprinted MNPs showed excellent specificity, in combination with high performance liquid chromatography, have been successfully applied to the selective separation and detection of chlorogenic acid and caffeic acid in TCMs.

Transformable Gallium-Based Liquid Metal Nanoparticles for Tumor Radiotherapy Sensitization.

The past decades have witnessed an increasing interest in the exploration of room temperature gallium-based liquid metal (LM) in the field of microfluidics, soft robotics, electrobiology, and biomedicine. Herein, this study for the first time reports the utilization of nanosized gallium-indium eutectic alloys (EGaIn) as a radiosensitizer for enhancing tumor radiotherapy. The sodium alginate (Alg) functionalized EGaIn nanoparticles (denoted as EGaIn@Alg NPs) are prepared via a simple one-step synthesis method. The coating of Alg not only prevents the aggregation and oxidation of EGaIn NPs in an aqueous solution but also enables them low cytotoxicity, good biocompatibility, and in-situ formation of gels in the Ca2+ enriched tumor physiological microenvironment. Due to the metallic nature and high density, EGaIn can increase the generation of reactive oxygen species under the irradiation of X-ray, which can not only directly promote DNA damage and cell apoptosis, but also show an efficient tumor inhibition rate in vivo. Moreover, EGaIn@Alg NPs hold good performance as computed tomography (CT) and photoacoustic tomography (PAT) imaging contrast agents. This work provides an alternative nanotechnology strategy for tumor radiosensitization and also enlarges the biomedical application of gallium-based LM.

Liquid-Crystal-Based Electrically Tuned Electromagnetically Induced Transparency Metasurface Switch.

In this study, a structure to realize a switchover between two different responses of electromagnetically induced transparency (EIT) was designed and implemented by simulation. Taking advantage of the anisotropy in the structure and the coupling between the radiative and dark elements, a metasurface switch with modulation depth of over 85% between orthogonal polarization incident light illuminations was demonstrated. The key mode switchover between the "on" and "off" states was achieved by electrically changing the dressing light polarization with a liquid crystals layer pre-aligned with a mature technology, without changing the incident light and an expected and reversible transition from an EIT-like spectrum to a strong spectral dip was observed. The modulation in the EIT switch fabricated with the proposed straightforward approach is a promising tool to control the groping velocity delay.