Plant-derived extracts have been used in various aspects of domestic life in recent years due to their significant antibacterial activity. Mesoporous silica nanomaterial (MSN) is a perfect adsorption carrier for the application of decorated blockboards due to the properties of temperature and pressure resistance. This work proposed a green and eco-friendly strategy of antibacterial decorated blockboards by loading MSN with plant-derived extracts as agents. We have successfully prepared uniform spherical mesoporous silica with an average particle size of 80.32 nm and adjustable specific surface area (530-866 cm2/g). The effective encapsulation of MSN allowed plantderived extracts to exhibit significant antibacterial effects against Escherichia coli and Staphylococcus aureus on the decorated blockboards. The MSN had the best loading content for the matrine, which can reach 22.7 %. Moreover, the loading discrepancy and adsorption paths of MSN on well-versed plant-derived extracts, e.g. catechin, matrine, and citral, was profoundly explored. A dual path adsorption theory involving physical adsorption through Van Der Waals force and chemical adsorption through hydrogen bonding networks or chemical bonding has been proposed by multi-representational methods. The results showed that the chemical adsorption of catechin was slightly stronger than the physical adsorption, accounting for 55.6 % of the total loading content. The physical adsorption of matrine and citral was more dominant, accounting for 60 % and 68.7 % of the total loading content, respectively.
Adenosine triphosphate (ATP) actively involve into cellular processes. Abnormal levels of ATP related to a variety of diseases, therefore determining the ATP level is of pivotal significance for diagnoses. Here, a highly sensitive fluorescence probe based on gold nanoclusters (Au NCs) was constructed for the detection of ATP, and an expanded detection range and low limit of detection (LOD) were realized in our work. Zeolitic imidazolate framework-8 (ZIF-8) enhanced the fluorescence intensity of Au NCs by the encapsulation and less ATP cause to a stronger fluorescence change, which guaranteed detection reproducibility and facilitated lower LOD. The LOD of Au NCs encapsulated ZIF-8 (AZ) for ATP detection was expanded to 2 μM, which was only 0.05 % of sole Au NCs (4000 μM). Significantly, ATP of high concentration quenched AZ by disrupting the structure of ZIF-8 which expanded the detection range. Moreover, the linear range of high concentration ATP detection in serum was 600-4000 μM, which was closed to the normal level of ATP in physiological. Therefore, due to its low LOD and high sensitivity, AZ can be applied for fluorescence detection and initial diagnosis of disease related to ATP.
A diabetic foot ulcer (DFU) is a common and serious complication of diabetes. This complication can result in amputation and death because of the several challenges associated with wound healing that can be attributed to the complex wound microenvironment, including biofilm infection, hyperglycemia, and diabetic angiopathy. Existing investigations on the wound-healing rate consider only one or two pathogenic factors, and therefore, despite the extensive research on these pathological microenvironments, there is an urgent need to optimize the wound-healing rate in patients with diabetic foot ulcers. To this end, a multitasking asynchronous collaborative nanosystem is designed in this study. The designed nanosystem can efficiently clear biofilm infections using optimized photodynamic therapy based on a poly photosensitizer ionic liquid (i.e., Ce6IL), reduce local blood glucose concentration using glucose oxidase, and reconstruct blood vessels by stimulating endothelial cell proliferation and migration using nitric oxide. The experimental results indicate that the three-step sequential collaboration strategy for clearing biofilm infections, reducing glucose concentrations, and reconstructing damaged blood vessels can help significantly accelerate wound healing rate in patients with diabetic foot ulcers.
Microwave hyperthermia (MH) is an emerging treatment for solid tumors, such as breast cancer, due to its advantages of minimally invasive and deep tissue penetration. However, MH induced tumor hypoxia is still an obstacle to breast tumor treatment failure. Therefore, an original nanoengineering strategy was proposed to exacerbate hypoxia in two stages, thereby amplifying the efficiency of activating tirapazamine (TPZ). And a novel microwave-sensitized nanomaterial (GdEuMOF@TPZ, GEMT) is designed. GdEuMOF (GEM) nanoparticles are certified excellent microwave (MW) sensitization performance, thus improving tumor selectivity to achieve MH. Meanwhile MW can aggravate the generation of thrombus and caused local circulatory disturbance of tumor, resulting in the Stage I exacerbated hypoxia environment passively. Due to tumor heterogeneity and uneven hypoxia, GEMT nanoparticles under microwave could actively deplete residual oxygen through the chemical reaction, exacerbating hypoxia level more evenly, thus forming the Stage II of exacerbated hypoxia environment. Consequently, a two-stage exacerbated hypoxia GEMT nanoparticles realize amplifying activation of TPZ, significantly enhance the efficacy of microwave hyperthermia and chemotherapy, and effectively inhibit breast cancer. This research provides insights into the development of progressive nanoengineering strategies for effective breast tumor therapy.
Zeolite imidazole framework-8 (ZIF-8) is the most prestigious one among zeolitic imidazolate framework (ZIF) with tunable dimensions and unique morphological features. Utilizing its synthetic adjustability and structural regularity, ZIF-8 exhibits enhanced flexibility, allowing for a wide range of functionalities, such as loading of nanoparticle components while preserving biomolecules activity. Extensive efforts are made from investigating synthesis techniques to develop novel applications over decades. In this review, the development and recent progress of various synthesis approaches are briefly summarized. In addition, its interesting properties such as adjustable porosity, excellent thermal, and chemical stabilities are introduced. Further, five representative biomedical applications are highlighted based on above physicochemical properties. Finally, the remaining challenges and offered insights into the future outlook are also discussed. This review aims to understand the co-relationships between structures and biomedical functionalities, offering the opportunity to construct attractive materials with promising characteristics.
Microwave (MW) dynamic therapy (MDT) can efficiently eliminate tumor residue resulting from MW thermal therapy. However, MDT is currently in its infancy, and luck of effective MDT sensiters severely limits its clinical therapeutic effect. Herein, based on TiMOF (TM), a high-efficiency MW sensitizer is designed for MW thermo-dynamic therapy. TM can generate heat and cytotoxic reacyive oxygen species (ROS) under MW irradiation and has the potential to be used as an MW sensitizer, while the suboptimal MW dynamic sensitization effect of TM limits its application. Inorder to improve the MW dynamic sensitization performance, a covalent organic framework (COF) with good stability and a large conjugate system is used to cover TM, which is conductive to electron and energy transfer, thus increasing the ROS generation rate and prolonging the ROS lifetime. In addition, loading Ni NPs endow nanomaterials with magnetic resonance imaging capabilities. Therefore, this work develops an MW sensitizer based on TM for the first time, and the mechanism of COF coating to enhance the MW dynamic sensitization of TM is preliminarily explored, which provides a new idea for the further development of MW sensitizer with great potential.
Backgrounds The novel concept of microwave dynamic therapy (MDT) solves the problem of incomplete tumor eradication caused by non-selective heating and uneven temperature distribution of microwave thermal therapy (MWTT) in clinic, but the poor delivery of microwave sensitizer and the obstacle of tumor hypoxic microenvironment limit the effectiveness of MDT. Results Herein, we engineer a liquid metal-based nanozyme LM@ZIF@HA (LZH) with eutectic Gallium Indium (EGaIn) as the core, which is coated with CoNi-bimetallic zeolite imidazole framework (ZIF) and hyaluronic acid (HA). The flexibility of the liquid metal and the targeting of HA enable the nanozyme to be effectively endocytosed by tumor cells, solving the problem of poor delivery of microwave sensitizers. Due to the catalase-like activity, the nanozyme catalyze excess H 2 O 2 in the tumor microenvironment to generate O 2 , alleviating the restriction of the tumor hypoxic microenvironment and promoting the production of ROS under microwave irradiation. In vitro cell experiments, the nanozyme has remarkable targeting effect, oxygen production capacity, and microwave dynamic effect, which effectively solves the defects of MDT. In the constructed patient-derived xenograft (PDX) model, the nanozyme achieves excellent MDT effect, despite the heterogeneity and complexity of the tumor model that is similar to the histological and pathological features of the patient. The tumor volume in the LZH + MW group is only about 1/20 of that in the control group, and the tumor inhibition rate is as high as 95%. Conclusion The synthesized nanozyme effectively solves the defects of MDT, improves the targeted delivery of microwave sensitizers while regulating the hypoxic microenvironment of tumors, and achieves excellent MDT effect in the constructed PDX model, providing a new strategy for clinical cancer treatment.
Microwave (MW) thermal therapy has been widely used for the treatment of cancer in clinics, but it still shows limited efficacy and a high recurrence rate owing to non-selective heat delivery and thermo-resistance. Regulating glycolysis shows great promise to improve MW thermal therapy since glycolysis plays an important role in thermo-resistance, progression, metabolism, and recurrence. Herein, we developed a delivery nanosystem of shikonin (SK)-loaded and hyaluronic acid (HA)-modified hollow Fe-MOF (HFM), HFM@SK@HA, as an efficient glycolysis-meditated agent to improve the efficacy of MW thermal therapy. The HFM@SK@HA nanosystem shows a high SK loading capacity of 31.7 wt %. The loaded SK can be effectively released from the HFM@SK@HA under the stimulation of an acidic tumor microenvironment and MW irradiation, overcoming the intrinsically low solubility and severe toxicity of SK. We also find that the HFM@SK@HA can not only greatly improve the heating effect of MW in the tumor site but also mediate MW-enhancing dynamic therapy efficiency by catalyzing the endogenous H2O2 to generate reactive oxygen species (ROS). As such, the MW irradiation treatment in the presence of HFM@SK@HA in vitro enables a highly improved anti-tumor efficacy due to the combined effect of released SK and generated ROS on inhibiting glycolysis in cancer cells. Our in vivo experiments show that the tumor inhibition rate is up to 94.75% ± 3.63% with no obvious recurrence during the 2 weeks after treatment. This work provides a new strategy for improving the efficacy of MW thermal therapy.
In vivo monitoring of treatment response is of great significance for tumor therapy in clinical trials, but it remains a formidable challenge. Herein, we demonstrate a logic AND gate theranostic nanoagent that responds to the coexistence of endogenous and exogenous stimuli, namely HAuCl4@1-Tetradecanol@Gd-based metal-organic framework@SiO2 nanocomposites (APGS NCs). Upon microwave (MW) irradiation, HAuCl4 in the inner part of APGS NCs reacts with the tumor-associated glutathione (GSH). Subsequently, it transforms into an active luminescent form of Au@1-Tetradecanol@Gd-MOF@SiO2 nanocomposites (AuPGS NCs). The intensity of generated fluorescence is correlated with the tumor thermal-injury status. Thus, the generation of AuPGS NCs with high intensity fluorescence under the co-activation of MW and GSH can visualize the treatment effects during MW thermal therapy and instantly modulate the irradiation time and range for optimal outcomes. Hence, this logic gate controlled APGS NCs makes MW thermal therapy eliminate tumor cells completely. This research offers an effective strategy for the design and preparation of activatable theranostic nanoagents for precise tumor imaging and therapy.
Janus particles have been considered suitable for biomedicine owing to their asymmetric structure and unique properties. Although Janus particles have been applied in biosensing for dual-mode sensing, there are almost no reports for the detection of multiple indicators. In fact, many patients require different diagnoses, such as the examination of hepatogenic diseases in diabetics. Here, a Janus particle based on SiO2 was synthesized using a Pickering emulsion method. A novel strategy for detecting glucose and alpha-fetoprotein (AFP) based on different principles using this Janus particle was then constructed as a detection platform. Composed of adjustable dendritic silica loaded with gold nanoclusters (Au NCs) and glucose oxidase (GOx) and spherical SiO2 coupled with AFP antibody, this Janus fluorescent probe achieved the double detection of glucose and AFP. With the protection of dendritic silica, the enzyme temperature stability was enhanced. Moreover, the low limit of detection for glucose (0.5 μM in PBS and 2.5 μM in serum) and AFP (0.5 ng mL-1) illustrated the feasibility of the application of the Janus material in integrated detection. This work not only supported the use of a Janus fluorescent probe as a detection platform toward glucose and AFP but also showed the potential of Janus particles in integrated detection in the future.
Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy.
Microwave thermal therapy (MWTT) is one of the most potent ablative treatments known, with advantages like deep penetration, minimal invasion, repeatable operation, and low interference from bone and gas. However, microwave (MW) is not selective against tumors, and residual tumors after incomplete ablation will generate immunosuppression, ultimately making tumors prone to recurrence and metastasis. Herein, a nano-immunomodulator (Bi-MOF-l-Cys@PEG@HA, BMCPH) is proposed to reverse the immunosuppression and reactivate the antitumor immune effect through responsively releasing H2S in tumor cells for improving MWTT. Under MW irradiation, BMCPH will mediate MWTT to ablate tumors and release l-cysteine (l-Cys) to react with the highly expressed cystathionine β-synthase in tumor to generate H2S. The generated H2S can inhibit the accumulation of myeloid-derived suppressor cells (MDSCs) and promote the expression of cytotoxic T lymphocytes (CTLs). Moreover, Bi-MOF can also scavenge reactive oxygen species (ROS), a major means of MDSCs-mediated immunosuppression, to further weaken the immunosuppressive effect. Simultaneously, the surface-covered HA will gather CTLs around the tumor to enhance the immune response. This nano gas immunomodulator provides an idea for the sensitive and tunable release of unstable gas molecules at tumor sites. The strategy of H2S gas to reverse immunosuppression and reactivate antitumor immune response introduces a direction to reduce the risk of tumor recurrence and metastasis after thermal ablation.
Microwave (MW) hyperthermia is one of the safest and most efficient minimally invasive tumor treatment methods, it is restricted by the bottlenecks of the heat sink effect and ineffective immune activation. Herein, a multifunctional nano platform with the load of nano immune modulator bimetallic metal-organic framework (BM), tumor vessel destructive agent and prodrug for gas production is developed for improving MW hyperthermia. Specifically, the combretastatin A4 phosphate (CA4P) was a vessel destructive agent to reduce MW heat loss by destructing the tumor blood vessel. Moreover, the as designed BM can scavenge the endogenic reactive oxygen species, which is conducive to hydrogen sulfide gas (H2S) that produced by bismuth sulfide (Bi2S3) to activate immune cells. Our in vivo experimental results demonstrate the destruction of tumor blood vessels coupled with the activated immune system results in the remarkable antitumor effect. This study provides an efficient strategy to improve MW hyperthermia by a combination of vasculature-targeting therapy with systemic immunity.
Thermotherapy can directly kill tumor cells whilst being accompanied by immune-enhancing effects. However, this immune-enhancing effect suffers from insufficient expression of immune response factors (e.g., heat shock protein 70, HSP70), resulting in no patient benefiting due to the recurrence of tumor cells after thermotherapy. Herein, a nanoengineered strategy of programmed upregulating of the immune response factors for amplifying synergistic therapy is explored. Metal-organic frameworks nanoamplifiers (teprenone/nitrocysteine@ZrMOF-NH2 @L-menthol@triphenylphosphine, GGA/CSNO@ZrMOF-NH2 -LM-TPP nanoamplifier, and GCZMT nanoamplifier) achieve excellent microwave (MW) thermal-immunotherapy by programmed induction of HSP70 expression. After intravenous administration, GCZMT nanoamplifiers target the mitochondria, and then release nitric oxide (NO) under MW irradiation. NO inhibits the growth of tumor cells by interfering with the energy supply of cells. Subsequently, under the combination of MW, NO, and GGA, HSP70 expression can be programmed upregulated, which can induce the response of cytotoxic CD4+ T cells and CD8+ T cells, and effectively activate antitumor immunotherapy. Hence, GCZMT nanoamplifier-mediated MW therapy can achieve a satisfactory therapeutic effect with the tumor inhibition of 97%. This research offers a distinctive insight into the exploitation of metal-organic frameworks nanoamplifiers for enhanced tumor therapy, which provides a new approach for highly effective cancer treatment.
Methyl glycolate (MG) is a high value-added chemical intermediate and widely used in the fields of medicine, chemical industry, fodder and dyes. A series of CuAg/SiO2 catalysts were prepared by sol-gel method for hydrogenation of dimethyl oxalate to MG. The structure of catalysts was characterized by XRD, N2-physical adsorption, FT-IR, TEM, H2-TPR, and XPS, and the influence of Ag loading on catalytic performance was investigated. The 5Ag-Cu/SiO2 catalyst with Ag loading of 5% exhibited the best catalytic performance with DMO conversion of 83.7% and MG selectivity of 72.2%. The characterization results showed that introducing appropriate amount of Ag not only improved the dispersion of copper species, but also increased the content of Cu+, thereby improving the catalytic activity of CuAg/SiO2 catalysts. In addition, the electron transfer between Ag and Cu could effectively stabilize Cu+, and eventually improved the stability of the catalyst.
The presence of high content glutathione (GSH) provides an effective "protective shield" for tumor cells, which undoubtedly is a huge impediment to reactive oxygen species (ROS)-based treatment. Fortunately, divalent copper (Cu2+) can not only consume GSH, destroying the protection mechanism of GSH, but also can be reduced to Cu+ with excellent Fenton-like reaction activity. Hence, capitalizing on the properties of liquid metals, we introduced Cu with three different valances via an in situ replacement reaction. A stable core-shell liquid-metal based "Cu storage pool" was obtained. It can effectively deplete GSH within the cells, and simultaneously produce ·OH through a Fenton-like reaction, further improving the effect of chemodynamic therapy (CDT). Under microwave irradiation, it is also capable of producing a large amount of ROS to promote tumor treatment. In addition, the loading of ionic liquid endows LZC@IL nanoparticles with certain microwave heating performance, which is able to augment microwave thermal therapy (MWTT). With the combination of CDT, microwave dynamic therapy (MDT) and MWTT, LZC@IL has an excellent effect on tumor elimination. This work offers a new idea for the application of liquid metals and the combined treatment of tumors, which has potential application value.
CdS@MoS2 nanocomposites (NCs) were successfully prepared through a simple hydrothermal reaction. The morphology and structure of MoS2 nanoflowers on CdS nanorods could be regulated by the change of the mass percentage of MoS2. The adsorption efficiency and photocatalytic activity of CdS@MoS2 NCs were investigated by the adsorption and photocatalytic degradation of Rhodamine 6G. Interestingly, with the increase of MoS2 ratio in the NCs, the adsorption effect of CdS@MoS2 NCs increased significantly. These CdS@MoS2 NCs showed a strong ability to process Rhodamine 6G, and could deal with up to 95% Rhodamine 6G within 1 h. CdS@MoS2 nanocomposites with tunable shape were synthesized through a hydrothermal method and possess high performance in the removal of Rhodamine 6G
We design multifunctional CDDP-VPA@ZrMOF-Cys-PEG nanoparticles (CVZP NPs) based on the properties of valproic acid (VPA) that can downregulate the expression of vascular endothelial growth factor (VEGF) to reduce the drug resistance of tumor cells. In vivo experiments confirm that chemotherapy combined with microwave thermal therapy (MWTT) can significantly improve the therapeutic effect of cisplatin-resistant lung cancer.
Microwave (MW) thermal therapy has been vigorously developed in recent years because of its better therapeutic efficiency and smaller side effects compared with traditional tumor treatment methods. In order to promote the tumor cell apoptosis under MW irradiation and achieve better therapeutic effect and prognosis, various microwave sensitizers have been developed. Metal organic frameworks (MOFs) have become one of the most popular materials for microwave sensitization due to their diverse morphology, porous surface and good biodegradability. However, the harsh preparation conditions and long growth time are insurmountable shortcomings of MOFs. Besides, the spongy porous structure of MOFs is not conducive to the retention of ions, leading to insufficient friction and collision between ions under MW radiation. Herein, we synthesized a kind of open-mouthed Zr MOF-derived nano-popcorns (ZDNPs) with the size of about 250 nm by a rapid sonochemical aerosol flow strategy. Compared with UIO-66, the open-mouthed ZDNPs have a better ability to entrap more ions due to their big cracks on the surface, thus improving their MW sensitization performance. The MW heating experiments in vitro present that the net temperature change value of ZDNP was 120% higher than UIO-66 at the same concentration, proving that ZDNP had a higher MW-thermo conversion efficiency than UIO-66, which provided an unprecedented direction for the exploration of more diversified MW sensitizers.
In this work,polymethacrylic acid(PMAA)-templated silver nanoclusters(Ag NCs) were developed as the fluorescent probe for the efficient and sensitive detection of adenosine triphosphate(ATP) in a wide range of pH values.The fluorescence intensity of the Ag NCs could keep stable with pH values ranging from2.5 to 9.3.The detection of ATP was based on the quenching of the fluorescent Ag NCs in the presence of ATP.The fluorescence quenching of the Ag NCs with increasing ATP concentration was studied at pH 2.5,4.5,7.0 and 8.5 which involved a wide pH environment in body fluids.The limit of detection(LOD) for ATP was as low as 0.1 mmol/L in an acidic environment with pH of 2.5 and all the linear correlation coefficients were satisfactory under wide-span pH values from 2.5 to 8.5.In addition,the sensitive determination of ATP was also achieved by adding copper ions(Cu 2+ ).The high selectivity and rapid detection process proved that the fluorescent probe had great potential to detect ATP in biological samples under different pH conditions.