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1.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38829219

ABSTRACT

In this article, we present a transient temperature detection device for silicon carbide (SiC) Schottky barrier diodes (SBDs) based on thermal reflection theory. We constructed a thermal reflection temperature measurement device based on a 530-nm green laser. This device is more suitable for transient temperature measurement of SiC SBDs than previous thermal reflection equipment. The accuracy of temperature measurement by our device was confirmed by comparison with the results of infrared thermal imaging. The high temporal resolution characteristics of the thermal reflection technology allowed the detection of millisecond-level transient temperature changes in SiC SBDs. In addition, we investigated the complementarity of transient temperature change curves during heating and cooling processes, as well as the reasons for the differences between these curves. Finally, we used the structural function method combined with the Bayesian deconvolution algorithm to obtain the thermal resistance along the heat flow path of the device and validated the results using an established thermal resistance testing method.

2.
Biomaterials ; 309: 122609, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38754290

ABSTRACT

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Drug Delivery Systems , Drug Resistance, Neoplasm , Lipid Metabolism , Mitochondria , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cholangiocarcinoma/metabolism , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Humans , Drug Resistance, Neoplasm/drug effects , Lipid Metabolism/drug effects , Cell Line, Tumor , Mice , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/metabolism , CD36 Antigens/metabolism , Metal-Organic Frameworks/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Nude , Reactive Oxygen Species/metabolism , Mice, Inbred BALB C , Lipase/metabolism
3.
Bioact Mater ; 36: 376-412, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38544737

ABSTRACT

The treatment of digestive system tumors presents challenges, particularly in immunotherapy, owing to the advanced immune tolerance of the digestive system. Nanomaterials have emerged as a promising approach for addressing these challenges. They provide targeted drug delivery, enhanced permeability, high bioavailability, and low toxicity. Additionally, nanomaterials target immunosuppressive cells and reshape the tumor immune microenvironment (TIME). Among the various cells in the TIME, tumor-associated macrophages (TAMs) are the most abundant and play a crucial role in tumor progression. Therefore, investigating the modulation of TAMs by nanomaterials for the treatment of digestive system tumors is of great significance. Here, we present a comprehensive review of the utilization of nanomaterials to modulate TAMs for the treatment of gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer. We also investigated the underlying mechanisms by which nanomaterials modulate TAMs to treat tumors in the digestive system. Furthermore, this review summarizes the role of macrophage-derived nanomaterials in the treatment of digestive system tumors. Overall, this research offers valuable insights into the development of nanomaterials tailored for the treatment of digestive system tumors.

4.
Int J Biol Macromol ; 265(Pt 2): 130891, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38493821

ABSTRACT

Avena sativa L. (A. sativa L.), commonly known as oat, is a significant cereal grain crop with excellent edible and medicinal value. Oat polysaccharides (OPs), the major bioactive components of A. sativa L., have received considerable attention due to their beneficial bioactivities. However, the isolation and purification methods of OPs lack innovation, and the structure-activity relationship remains unexplored. This review emphatically summarized recent progress in the extraction and purification methods, structural characteristics, biological activities, structure-to-function associations and the potential application status of OPs. Different materials and isolation methods can result in the differences in the structure and bioactivity of OPs. OPs are mainly composed of various monosaccharide constituents, including glucose, arabinose and mannose, along with galactose, xylose and rhamnose in different molar ratios and types of glycosidic bonds. OPs exhibited a broad molecular weight distribution, ranging from 1.34 × 105 Da to 4.1 × 106 Da. Moreover, structure-activity relationships demonstrated that the monosaccharide composition, molecular weight, linkage types, and chemical modifications are closely related to their multiple bioactivities, including immunomodulatory activity, antioxidant effect, anti-inflammatory activity, antitumor effects etc. This work can provide comprehensive knowledge, update information and promising directions for future exploitation and application of OPs as therapeutic agents and multifunctional food additives.


Subject(s)
Avena , Polysaccharides , Polysaccharides/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Monosaccharides/chemistry , Food Additives
5.
Ecotoxicol Environ Saf ; 273: 116127, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38394756

ABSTRACT

Alkaline stress poses a significant challenge to the healthy growth of fish. Ginger polysaccharide (GP) is one of the main active substances in ginger and has pharmacological effects, such as anti-oxidation and immune regulation. However, the physiological regulatory mechanism of GP addition to diet on alkalinity stress in crucian carp remains unclear. This study aimed to investigate the potential protective effects of dietary GP on antioxidant capacity, gene expression levels, intestinal microbiome, and metabolomics of crucian carp exposed to carbonate (NaHCO3). The CK group (no GP supplementation) and COG group (NaHCO3 stress and no GP supplementation) were set up. The GPCS group (NaHCO3 stress and 0.4% GP supplementation) was stressed for seven days. Based on these data, GP significantly increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), acid phosphatase (ACP), and alkaline phosphatase (AKP) in carp under alkalinity stress (p < 0.05) and decreased the activity of malon dialdehyde (MDA) (p < 0.05). GP restored the activity of GSH-PX, ACP, and AKP to CK levels. The expression levels of tumor necrosis factor ß (TGF-ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 8 (IL-8) genes were decreased, and the expression levels of determination factor kappa-B (NF-κB) and interleukin 10 (IL-10) genes were increased (p < 0.05). Based on 16 S rRNA high-throughput sequencing, GP improved the changes in the intestinal microbial diversity and structural composition of crucian carp caused by NaHCO3 exposure. In particular, GP increased the relative abundance of Proteobacteria and Bacteroidetes and decreased the relative abundance of Actinobacteria. The metabolic response of GP to NaHCO3 exposed crucian carp guts was studied using LC/MS. Compared to the COG group, the GPCS group had 64 different metabolites and enriched 10 metabolic pathways, including lipid metabolism, nucleotide metabolism, and carbohydrate metabolism. The addition of GP to feed can promote galactose metabolism and provide an energy supply to crucian carp, thus alleviating the damage induced by alkalinity stress. In conclusion, GP can mitigate the effects of NaHCO3 alkalinity stress by regulating immune function, intestinal flora, and intestinal metabolism in crucian carp. These findings provide a novel idea for studying the mechanism of salt-alkali tolerance in crucian carp by adding GP to feed.


Subject(s)
Carps , Gastrointestinal Microbiome , Zingiber officinale , Animals , Goldfish/metabolism , Carps/metabolism , Antioxidants/metabolism , Diet , Carbonates , Animal Feed/analysis
6.
ACS Nano ; 18(4): 3636-3650, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38227493

ABSTRACT

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.


Subject(s)
Cockayne Syndrome , Neoplasms , Humans , Microwaves , Energy Transfer
7.
J Colloid Interface Sci ; 659: 178-190, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38163404

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Hyperthermia, Induced , Neoplasms , Humans , Female , Tirapazamine/pharmacology , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Microwaves , Neoplasms/therapy , Hypoxia/therapy , Cell Line, Tumor
8.
Bioact Mater ; 33: 532-544, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38162511

ABSTRACT

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

9.
Int J Biol Macromol ; 257(Pt 1): 128565, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38061516

ABSTRACT

Portulaca oleracea L., also known as purslane, affiliates to the Portulacaceae family. It is an herbaceous succulent annual plant distributed worldwide. P. oleracea L. is renowned for its nutritional value and medicinal value, which has been utilized for thousands of years as Traditional Chinese Medicine (TCM). The extract derived from P. oleracea L. has shown efficacy in treating various diseases, including intestinal dysfunction and inflammation. Polysaccharides from P. oleracea L. (POP) are the primary constituents of the crude extract which have been found to have various biological activities, including antioxidant, antitumor, immune-stimulating, and intestinal protective effects. While many publications have highlighted on the structural identification and bioactivity evaluation of POP, the underlying structure-activity relationship of POP still remains unclear. In view of this, this review aims to focus on the extraction, purification, structural features and bioactivities of POP. In addition, the potential structure-activity relationship and the developmental perspective for future research of POP were also explored and discussed. The current review would provide a valuable research foundation and the up-to-date information for the future development and application of POP in the field of the functional foods and medicine.


Subject(s)
Portulaca , Portulaca/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Plant Extracts , Nutritive Value
10.
Small Methods ; 8(3): e2301270, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37997211

ABSTRACT

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.


Subject(s)
Nanoparticles , Zeolites , Zeolites/chemistry , Nanoparticles/chemistry , Porosity
11.
J Ethnopharmacol ; 323: 117688, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38159827

ABSTRACT

ETHNOPHARMACOLOGIC RELEVANCE: Crataegus pinnatifida, commonly known as hawthorn, is a plant species with a long history of medicinal use in traditional Chinese medicine. Hawthorn polysaccharides (HP) have gained worldwide attention due to their decent biological activities and potential health benefits. Their excellent antioxidant activity, antitumor activity, immunomodulatory activity, hypoglycemic effect and hypolipidemic effects, intestinal microbiota modulatory activity makes them valuable in the field of ethnopharmacological research. AIM OF THE STUDY: The purpose of the current review is to provide a systematic and comprehensive summary of the latest literatures and put forward the future perspectives on hawthorn polysaccharides in the context of its extraction, purification, structural characteristics and bioactivities. Furthermore, the underlying structure-bioactivity relationship of hawthorn polysaccharides was also explored and discussed. The current review would provide the important research underpinnings and the update the information for future development and application of hawthorn polysaccharides in the pharmaceutical and functional food industries. MATERIALS AND METHODS: We use Google Scholar, CNKI, PubMed, Springer, Elsevier, Wiley, Web of Science and other online databases to search and obtain the literature on extraction, isolation, structural analysis and the biological activity of hawthorn polysaccharides published before October 2023. The key words are "extraction", "isolation and purification", "bioactivities", and "Crataegus pinnatifida polysaccharides ". RESULTS: Crataegus pinnatifida has been widely used for the treatment of cardiovascular diseases, digestive disorders, inflammatory and oxidative stress in traditional Chinese medicine. Polysaccharides are the key active components of Crataegus pinnatifida which have gained widespread attention. The structure and bioactivity of polysaccharides from Crataegus pinnatifida varies in terms of raw materials, extraction methods and purification techniques. Crataegus pinnatifida polysaccharides possess diverse bioactivities, including antitumor, immunomodulatory, hypoglycemic activity, cardioprotective and antioxidant activities, among others. These biological properties can not only lay firm foundation for the treatment of diverse diseases, but also provide a theoretical basis for the in-depth study of the structure-activity relationship. In addition, the underlying structure-activity relationship is also explored and discussed, and further research and development of hawthorn polysaccharides are also prospected. CONCLUSION: As a natural compound, hawthorn polysaccharides has garnered significant attention and held immense research potential. Hawthorn polysaccharides can be obtained through different extraction methods, including hot water extraction method, ultrasonic extraction method and enzymatic extraction method etc. The structures of hawthorn polysaccharides have also been characterized and reported in numerous studies. Moreover, hawthorn polysaccharides exhibit a wide range of bioactivities, such as the antioxidant activity, the antitumor activity, the immunomodulatory activity, the hypoglycemic effect and the hypolipidemic effect, as well as the intestinal microbiota modulatory activity. These diverse bioactivities contribute to the growing interest in hawthorn polysaccharides and its potential applications. Hawthorn polysaccharides has promising application prospects in various industries, including functional food, pharmaceuticals and biomedical research. Therefore, it is imperative to fully explore and harness the potential of hawthorn polysaccharides in the food and medicine fields.


Subject(s)
Crataegus , Crataegus/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/chemistry , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Plant Extracts/pharmacology , Hypoglycemic Agents
12.
ACS Nano ; 17(24): 25575-25590, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38095158

ABSTRACT

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.


Subject(s)
Metal-Organic Frameworks , Triple Negative Breast Neoplasms , Humans , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/therapeutic use , Microwaves , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Programmed Cell Death 1 Receptor , Phosphatidylinositol 3-Kinases , Immunosuppressive Agents/pharmacology , Tumor Microenvironment , Immunotherapy , Cell Line, Tumor
13.
Small ; : e2308055, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38037766

ABSTRACT

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.

14.
ACS Nano ; 17(19): 19242-19253, 2023 10 10.
Article in English | MEDLINE | ID: mdl-37781935

ABSTRACT

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.


Subject(s)
Microwaves , Neoplasms , Humans , Microwaves/therapeutic use , Immunosuppression Therapy , Neoplasms/therapy , Immunity , Immune Tolerance , Tumor Microenvironment
15.
J Nanobiotechnology ; 21(1): 399, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37904235

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Microwaves , Hydrogen Peroxide , Neoplasms/drug therapy , Metals/therapeutic use , Cell Line, Tumor , Tumor Microenvironment
16.
Acta Biomater ; 172: 382-394, 2023 12.
Article in English | MEDLINE | ID: mdl-37797707

ABSTRACT

Microwave (MW) thermal therapy has been developed as an effective clinical strategy that can achieve pronounced antitumor activity and also has the potential to trigger antitumor immunity. However, patients generally face high rates of tumor recurrence following MW treatment, limiting the long-term benefits of such treatment. The combination of MW treatment and immunomodulatory strategies may represent a promising means of reprogramming the immunosuppressive tumor microenvironment (TME) in a manner conducive to lower recurrence rates. In this study, a Lenvatinib-loaded Gd/Fe metal-organic framework (Gd/FeMOF) was designed as a promising approach to enhancing such antitumor immunity. MW-enhanced dynamic Gd/FeMOF sensitization can facilitate high levels of reactive oxygen species production under MW irradiation, resulting in stronger immunogenic tumor cell death. In parallel, the Lenvatinib released from Gd/FeMOF preparations can serve as an immune adjuvant that suppresses programmed death ligand 1 (PD-L1) expression and drives the reprogramming of the immunosuppressive TME. The Gd and Fe present within this MOF preparation also imbue it with magnetic resonance imaging capabilities. Importantly, in vivo animal model experiments confirmed the ability of GdFeMOF treatment to significantly enhance antitumor immunity while protecting against recurrence. Accordingly, this study offers a foundation for promising strategies aimed at the integrated diagnosis and durable treatment of cancer. STATEMENT OF SIGNIFICANCE: High rates of tumor recurrence following MW thermal therapy limit the long-term benefits of such treatment. We found that the administration of Lenvatinib-loaded Gd/FeMOF nanoparticles significantly reduced tumor recurrence after MW thermal therapy. Under MW irradiation, the Gd/FeMOF nanoparticles were found to augment the immune response due to facilitation of the process of immunogenic cell death. In addition, the released Lenvatinib could act as an immune adjuvant to downregulate the expression of PD-L1 and reprogram the immunosuppressive state of the tumor microenvironment, thus further enhancing the immune response. This is significant because MW-induced immune responses are relatively weak and usually fail to effectively prevent tumor recurrence. The combination of MW treatment with an immunomodulatory strategy may solve this problem.


Subject(s)
B7-H1 Antigen , Neoplasms , Animals , Humans , Microwaves , Neoplasm Recurrence, Local , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/metabolism , Tumor Microenvironment
17.
Biomaterials ; 302: 122299, 2023 11.
Article in English | MEDLINE | ID: mdl-37673000

ABSTRACT

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.


Subject(s)
Neoplasms , Precision Medicine , Humans , Microwaves , Silicon Dioxide , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Theranostic Nanomedicine/methods , Cell Line, Tumor
18.
ACS Biomater Sci Eng ; 9(9): 5405-5417, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37638660

ABSTRACT

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.


Subject(s)
Iron , Metal Nanoparticles , Metal-Organic Frameworks , Naphthoquinones , Neoplasms , Metal-Organic Frameworks/chemistry , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Neoplasms/therapy , Iron/chemistry , Naphthoquinones/administration & dosage , Naphthoquinones/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Microwaves/therapeutic use , Warburg Effect, Oncologic/drug effects , Hep G2 Cells , Cell Line, Tumor , L Cells , Female , Animals , Mice , Humans
19.
Front Psychol ; 14: 1226661, 2023.
Article in English | MEDLINE | ID: mdl-37645068

ABSTRACT

Introduction: Adults possess a natural inclination to associate sensory cues derived from distinct modalities, such as the pairing of sweet with pink. However, studies exploring crossmodal correspondences in children, particularly in the sensory pairing of visual features and tastes, are scant, leaving unanswered questions regarding the developmental trajectory of crossmodal correspondences. The present study investigates whether Japanese preschool children demonstrate specific biases in shape-color, shape-taste, and color-taste associations. Methods: In a series of in-person experiments, 92 children between 3 to 6 years of age completed matching tasks utilizing paper stimuli. Results: Children exhibit crossmodal correspondences in shape-color (circle-red and asymmetrical star-yellow), shape-taste (triangle-salty and circle-sweet), and color-taste (yellow-sour, black-bitter, and pink-sweet) associations. Moreover, children's choices are not influenced by their individual preferences. Discussion: The crossmodal correspondences observed in this study have been observed in previous research on adults from the same (Japanese) culture, although adults showed more crossmodal correspondences than the children in this study (e.g., pink-circle, triangle-sour, and green-bitter). Thus, while some crossmodal correspondences emerge during childhood, others may require additional time to develop, thereby highlighting the importance of understanding the cognitive mechanisms underlying crossmodal correspondences from an ontogenic perspective.

20.
J Nanobiotechnology ; 21(1): 250, 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37533106

ABSTRACT

Nano-engineering with unique "custom function" capability has shown great potential in solving technical difficulties of nanomaterials in tumor treatment. Through tuning the size and surface properties controllablly, nanoparticles can be endoewd with tailored structure, and then the characteristic functions to improve the therapeutic effect of nanomedicines. Based on nano-engineering, many have been carried out to advance nano-engineering nanomedicine. In this review, the main research related to cancer therapy attached to the development of nanoengineering nanomedicines has been presented as follows. Firstly, therapeutic agents that target to tumor area can exert the therapeutic effect effectively. Secondly, drug resistance of tumor cells can be overcome to enhance the efficacy. Thirdly, remodeling the immunosuppressive microenvironment makes the therapeutic agents work with the autoimmune system to eliminate the primary tumor and then prevent tumor recurrence and metastasis. Finally, the development prospects of nano-engineering nanomedicine are also outlined.


Subject(s)
Nanoparticles , Neoplasms , Humans , Nanomedicine , Neoplasms/therapy , Drug Delivery Systems , Nanoparticles/chemistry , Immunosuppressive Agents/pharmacology , Tumor Microenvironment
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