RESUMO
Water scarcity is a global problem and collecting water from the air is a viable solution to this crisis. Inspired by Namib Desert beetle, leaf venation and spider silk, we designed an integrated biomimetic system with hybrid wettability and wettability gradient. The hybrid hydrophilic-hydrophobic wettability design that bionomics desert beetle's back can construct a three-dimensional topography with a water layer on the surface, expanding the contact area with the fog flow and thus improving the droplet trapping efficiency. The venation-like structure with wettability gradient not only provides a planned path for water transportation, but also accelerates water removal under the synergistic effect of gravity and wettability driving force, thus further improving the surface regeneration rate. The collector combines droplet capture, coalescence, transportation, separation, and storage capabilities, which provides new ideas for the design of future high-efficiency fog collectors.
RESUMO
Superwetting surfaces are often applied in oil/water separation. Hydrogels have been widely prepared as superhydrophilic/underwater superoleophobic materials for oil/water separation since they are naturally hydrophilic. Hydrogels usually need to be combined with porous substrates such as stainless steel mesh (SSM) due to their poor mechanical properties. However, it is usually inevitable that the pores of the substrate are clogged during the actual preparation process, leading to a significant decrease in the flux, which limits its effective application. In this study, acrylic acid (AA), chitosan (CS) and modified silica were utilized to form a layer of dual-network PAA/CS@SiO2 hydrogel by photopolymerization on SSM, followed by a simple and novel ultrasonic-assisted pore-making method to generate numerous pores in situ on the surface of the hydrogel-coated mesh, which led to an increase in water flux from 0 to 70,000 L m-2 h-1 without decreasing the separation efficiency. After 100 separations of a mixture of n-hexane and water, the flux was still higher than 50,000 L m-2 h-1 with a separation efficiency above 99%, which is superior to most of hydrogel-coated meshes reported so far. Moreover, the prepared PAA/CS@SiO2 hydrogel-coated mesh also has good environmental stability, low swelling, and self-cleaning properties. We believe that the strategy of this study will provide a simple new perspective when hydrogels block the substrate pores, resulting in low water flux.
RESUMO
Adsorption-based atmospheric water harvesting (AWH) with solar-driven photothermal desorption has become an effective means of solving freshwater scarcity in arid regions due to its low energy consumption and high efficiency. Moisture adsorption and desorption capacities are the most critical properties in AWH, and it is a challenge to improve the rate of moisture adsorption and desorption of composite adsorbents. Therefore, this paper reports a SA/carboxymethyl chitosan (CCS)/C/CaCl2-U composite aerogel adsorbents with simultaneously green, low-cost, degradable, and fast hygroscopicity and desorption kinetics. The composite adsorbent used water-soluble biomass materials sodium alginate (SA) and carboxymethyl chitosan (CCS) as the backbone of the aerogel, constructed a vertically aligned unidirectional pore structure by directional freezing, and introduced nanocarbon powder and moisture-absorbent salt calcium chloride (CaCl2) to improve the solar photothermal performance and water absorption, respectively. The results showed that the composite adsorbent had good water uptake capacity at 30-90% relative humidity (RH), the time to reach the water uptake of 1 g g-1 at 90% RH was only 2.5 h, and the final water uptake rate was up to 1.9 g g-1 within 12 h. Meanwhile, the composite sorbent can be heated and desorbed basically within 1 h at 80 °C and its evaporation efficiency is 1.3 times higher than that of the aerogel sorbent prepared by the conventional method when irradiated with 1000 W m-2 light intensity for 2 h. Therefore, the SA/CCS/C/CaCl2-U composite aerogel adsorbent of this study has a potential that can be applied in AWH due to its environmental friendliness, low cost, and faster hygroscopic desorption kinetics.
RESUMO
Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.
Assuntos
Síndrome de Cockayne , Neoplasias , Humanos , Micro-Ondas , Transferência de EnergiaRESUMO
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.
Assuntos
Antineoplásicos , Neoplasias da Mama , Hipertermia Induzida , Neoplasias , Humanos , Feminino , Tirapazamina/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Micro-Ondas , Neoplasias/terapia , Hipóxia/terapia , Linhagem Celular TumoralRESUMO
Microwave thermotherapy (MWTT) has limited its application in the clinic due to its high rate of metastasis and recurrence after treatment. Nitric oxide (NO) is a gaseous molecule that can address the high metastasis and recurrence rates after MWTT by increasing thermal sensitivity, down-regulating the expression of hypoxia-inducible factor-1 (HIF-1), and inducing the immunogenic cell death (ICD). Therefore, GaMOF-Arg is designed, a gallium-based organic skeleton material derivative loaded with L-arginine (L-Arg), and coupled the mitochondria-targeting drug of triphenylphosphine (TPP) on its surface to obtain GaMOF-Arg-TPP (GAT) MW-immunosensitizers. When GAT MW-immunosensitizers are introduced into mice through the tail vein, reactive oxygen species (ROS) are generated and L-Arg is released under MW action. Then, L-Arg reacts with ROS to generate NO, which not only downregulates HIF-1 expression to improve tumor hypoxia exacerbated by MW, but also enhances immune responses by augment calreticulin (CRT) exposure, high mobility group box 1 (HMGB1) release, and T-cell proliferation to achieve prevention of tumor metastasis and recurrence. In addition, NO can induce mitochondria damage to increase their sensitivity to MWTT. This study provides a unique insight into the use of metal-organic framework MW-immunosensitizers to enhance tumor therapy and offers a new way to treat cancer efficiently.
RESUMO
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.
Assuntos
Estruturas Metalorgânicas , Neoplasias de Mama Triplo Negativas , Humanos , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/uso terapêutico , Micro-Ondas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Receptor de Morte Celular Programada 1 , Fosfatidilinositol 3-Quinases , Imunossupressores/farmacologia , Microambiente Tumoral , Imunoterapia , Linhagem Celular TumoralRESUMO
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 H2O2 in the tumor microenvironment to generate O2, 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.
Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Micro-Ondas , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico , Metais/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
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 ß-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.
Assuntos
Micro-Ondas , Neoplasias , Humanos , Micro-Ondas/uso terapêutico , Terapia de Imunossupressão , Neoplasias/terapia , Imunidade , Tolerância Imunológica , Microambiente TumoralRESUMO
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.
Assuntos
Neoplasias , Medicina de Precisão , Humanos , Micro-Ondas , Dióxido de Silício , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neoplasias/patologia , Nanomedicina Teranóstica/métodos , Linhagem Celular TumoralRESUMO
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.
Assuntos
Ferro , Nanopartículas Metálicas , Estruturas Metalorgânicas , Naftoquinonas , Neoplasias , Estruturas Metalorgânicas/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Neoplasias/terapia , Ferro/química , Naftoquinonas/administração & dosagem , Naftoquinonas/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Micro-Ondas/uso terapêutico , Efeito Warburg em Oncologia/efeitos dos fármacos , Células Hep G2 , Linhagem Celular Tumoral , Células L , Feminino , Animais , Camundongos , HumanosRESUMO
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.
Assuntos
Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Micro-Ondas , Espécies Reativas de Oxigênio , Neoplasias/tratamento farmacológicoRESUMO
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.
Assuntos
Glucose , alfa-Fetoproteínas , Humanos , Corantes Fluorescentes , Dióxido de Silício/químicaRESUMO
BACKGROUNDS: Reversing the immunosuppressive tumor microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. RESULTS: Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the infiltration of the tumor-T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen (O2) levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce-Mn MOF nanoparticles coated with polydopamine. The Ce-Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O2 under microwave irradiation, resulting in overcoming hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Ce-Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. CONCLUSION: Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cell infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment.
Assuntos
Adjuvantes Imunológicos , Micro-Ondas , Cisplatino , Espécies Reativas de Oxigênio , Fatores Imunológicos , Imunossupressores , Imunoterapia , Oxirredução , Glutationa , OxigênioRESUMO
Hollow materials derived from metal-organic frameworks (MOFs) have emerged in the biomedical field due to their unique properties, and different synthesis methods have been proposed. However, so far, the large-scale use of hollow MOFs is mostly limited by the timeliness of synthesis methods. Herein, we propose a new ultrasonic aerosol flow strategy for the instantaneous synthesis of a Zr-MOF-derived hollow sphere complex (ZC-HSC) in only one step. Through rapid transient heating, the coordination between metal salts and organic ligands occurs along with prompt evaporation of the solvent. The whole process lasts for only about 21 s, compared with several steps that take hours or even days for conventional synthesis methods. Based on the ZC-HSC, we designed a nanodrug with the functions of manipulating the tumor microenvironment, which can reshape the tumor microenvironment by improving tumor hypoxia and inflammatory microenvironment and promoting antiangiogenic therapy. Combined with microwave thermo-chemotherapy, the nanodrugs effectively treat triple-negative breast cancer (the tumor cell survival rate was only 34.76 and 31.05% in normoxic and hypoxic states, respectively, and the tumor inhibition rate reached 87.9% at the animal level), providing a new theoretical basis for the treatment of triple-negative breast cancer. This rapid, one-step, and continuous ultrasonic aerosol flow strategy has bright prospects in the synthesis of MOF-derived hollow materials and promotes the further development of large-scale applications of biological nanomaterials.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Micro-Ondas , Estruturas Metalorgânicas/farmacologia , Microambiente Tumoral , Nanopartículas/uso terapêuticoRESUMO
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.
Assuntos
Estruturas Metalorgânicas , Linfócitos T CD8-Positivos , Proteínas de Choque Térmico HSP70RESUMO
Microwave hyperthermia is an emerging minimally invasive therapy in which thermal damage and apoptosis of tumor cells are induced by local heating of tissues with microwave radiation. Recently, microwave hyperthermia has been widely used in clinical practice; however, uneven aggregation and dispersion of malignant tumors after microwave hyperthermia are the main problems associated with this method. In this work, a microridged waveguide tumor hyperthermia antenna with an operating frequency of 915 MHz was designed. Although its volume is only 6.6 cm3, it exhibited a highly focused heating effect, achieving rapid heating in a small area. However, microwave hyperthermia has several shortcomings. Microwaves cannot specifically identify and target tumors; this decreases the efficiency of the treatment if the temperature of the tumor site is not sufficiently high for its size and location. Therefore, Zr metal-organic framework (ZrMOF)-derived composite ZCNC was synthesized using the ultrasonic aerosol flow method, which has good microwave sensitization and biosafety. ZCNC reduced the damage to normal cells and greatly improved the tumor treatment effect of microwave hyperthermia (tumor inhibition rate reached 78.01%). Thus, the proposed strategy effectively improves the current clinical microwave hyperthermia treatment method.
RESUMO
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.
Assuntos
Hipertermia Induzida , Estruturas Metalorgânicas , Neoplasias , Humanos , Hipertermia , Hipertermia Induzida/métodos , Micro-Ondas , Neoplasias/terapiaRESUMO
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.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Glutationa , Humanos , Peróxido de Hidrogênio , Micro-Ondas , Neoplasias/tratamento farmacológico , Espécies Reativas de OxigênioRESUMO
Microwave thermal therapy (MWTT) shows great prospect in cancer treatments due to its non-invasive or minimally invasive nature and deep penetration through the tissue. However, incomplete ablation and elevated expression of many pro-tumor angiogenesis after MWTT (e.g., vascular endothelial growth factor, VEGF) induced tumor recurrence still remains an obstacle, especially in some tumors prone to recurrence and metastasis, such as colorectal cancer. Herein, we propose a nanocapsule of covalent organic framework cladding metal organic framework (MOF@COF) with microwave (MW) thermal-dynamic sensitization and co-action of tumor anti-angiogenesis. The MOF of Bi-Mn-porphyrin (BM) is designed as MW sensitizer to generate cytotoxic 1O2 and heat for microwave dynamic therapy (MWDT) synergistic MWTT. The COF is covalently coated on BM for further augmenting these two sensitization properties, as well as loading hydrophobic inhibitor of Apatinib to downregulate the expression of VEGF for inhibiting tumor recurrence. Furthermore, the contained Bi and porphyrin endow system with CT and fluorescence imaging (FI) capabilities. In vivo experiments verify that this combination therapy significantly impairs the growth of colorectal cancer with no recurrent carcinoma. Therefore, our work presents an integrated strategy derived from MOF@COF for remarkably augmenting single MWTT to reduce tumor recurrence.