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1.
Medicine (Baltimore) ; 103(23): e38420, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847718

ABSTRACT

BACKGROUND: The aim of this study is to analyze the process and frontiers of research in myocardial bridges (MB) to identify future research directions in the last 3 decades. METHODS: Relevant literature on MB combined with myocardial infarction (MI) was searched from 1991 to 2023 in the Web of Science database, and was analyzed by bibliometric analysis using VOSviewer, CiteSpace, and the R package "bibliometrix." RESULTS: A total of 1233 English articles were included in this study. The number of published articles showed an increasing trend yearly. From 2017 to 2022, the annual publication volume rose rapidly, and in 2021 the publication volume even reached 95 articles, which was the highest in all years. These publications were from 68 countries and 1854 institutions, with the leading country being the U.S. and the leading institution being Columbia University. Myoho Clinical International has a close collaborative relationship with Columbia University, while in recent years, the Harvard Medical School has explored the study of MB combined with MI. Annals of Thoracic Surgery was the journal with the highest number of publications, and Takayama Hiroo and Naka Yoshifumi were the authors with the highest number of publications. The most common keywords were MI, cardiogenic shock, and MB. CONCLUSIONS: Our findings can help researchers explore the current status of MB combined with MI research and choose new survey routes for upcoming studies. Prevalence and prognosis, mechanism of MB combined with MI and molecular mechanism may become the focus of future research. In addition, more research and cooperation are needed worldwide.


Subject(s)
Bibliometrics , Myocardial Bridging , Myocardial Infarction , Humans , Myocardial Bridging/complications
2.
ACS Appl Mater Interfaces ; 16(20): 26288-26298, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38725121

ABSTRACT

Sulfide-based all-solid-state lithium batteries (ASSLBs) have attracted unprecedented attention in the past decade due to their excellent safety performance and high energy storage density. However, the sulfide solid-state electrolytes (SSEs) as the core component of ASSLBs have a certain stiffness, which inevitably leads to the formation of pores and cracks during the production process. In addition, although sulfide SSEs have high ionic conductivity, the electrolytes are unstable to lithium metal and have non-negligible electronic conductivity, which severely limits their practical applications. Herein, a grain boundary electronic insulation strategy through in situ polymer encapsulation is proposed for this purpose. A polymer layer with insulating properties is applied to the surface of the Li5.5PS4.5Cl1.5 (LPSC) electrolyte particles by simple ball milling. In this way, we can not only achieve a dense electrolyte pellet but also improve the stability of the Li metal anode and reduce the electronic conductivity of LPSC. This strategy of electronic isolation of the grain boundaries enables stable deposition/stripping of the modified electrolyte for more than 2000 h at a current density of 0.5 mA cm-1 in a symmetrical Li/Li cell. With this strategy, a full cell with Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) as the cathode shows high performance including high specific capacity, improved high-rate capability, and long-term stability. Therefore, this study presents a new strategy to achieve high-performance sulfide SSEs.

3.
Plant Physiol Biochem ; 212: 108767, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38797009

ABSTRACT

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

4.
Mater Today Bio ; 25: 101002, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38420141

ABSTRACT

Acute kidney injury (AKI) is a heterogeneous, high-mortality clinical syndrome with diverse pathogenesis and prognosis, but it lacks the effective therapy clinically. Its pathogenesis is associated with production of reactive oxygen/nitrogen species and infiltration of inflammatory cells. To overcome these pathogenic factors and improve the therapeutic efficiency, we synthesized triptolide-loaded mesoscale polydopamine melanin-mimetic nanoparticles (MeNP4TP) as the antioxidant plus anti-inflammatory therapeutic platform to synergistically scavenge reactive oxygen/nitrogen species (RONS), inhibit the activity of macrophages and dendritic cells, and generate Treg cells for AKI therapy. It was demonstrated that mesoscale size was beneficial for MeNP4TP to specifically accumulate at renal tubule cells, and MeNP4TP could significantly attenuate oxidative stress, reduce proinflammatory immune cells in renal, and repair renal function in cisplatin-induced AKI mouse model. MeNP4TP might be a potential candidate to inhibit oxidative damages and inflammatory events in AKI.

6.
Adv Healthc Mater ; 12(28): e2301343, 2023 11.
Article in English | MEDLINE | ID: mdl-37586109

ABSTRACT

Premetastatic niche (PMN) is a prerequisite for tumor metastasis. Destruction of PMN can significantly suppress the tumor metastasis. Bone marrow-derived cells are usually recruited into the premetastatic organs to support PMN formation, which can be orchestrated by tumor-derived secreted factors. Neutrophils can chemotactically migrate towards the inflammatory sites and consume tumor-derived secreted factors, capable of acting as therapeutic agents for a broad-spectrum suppression of PMN formation and metastasis. However, neutrophils in response to inflammatory signals can release neutrophil extracellular traps (NETs), promoting the tumor metastasis. Herein, live neutrophils are converted into dead neutrophils (C NE) through a quick-frozen process to maintain PMN-targeting and tumor-derived secreted factor-consuming abilities but eliminate NET-releasing shortcomings. Considering macrophages-regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) are further hitchhiked on the surface of C NE to form C NEMag , which can repolarize macrophages from M2 to M1 phenotype for further disruption of PMN formation. A series of in vitro and in vivo assessments have been applied to confirm the effectiveness of C NEMag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti-metastatic therapy in clinics.


Subject(s)
Extracellular Traps , Magnetosomes , Neoplasms , Humans , Neutrophils , Phenotype , Neoplasms/pathology
7.
Small ; 19(46): e2303073, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37460404

ABSTRACT

Glioblastoma (GBM), the most aggressive and lethal form of malignant brain tumor, is a therapeutic challenge due to the drug filtration capabilities of the blood-brain barrier (BBB). Interestingly, glioblastoma tends to resist apoptosis during chemotherapy, but is susceptible to ferroptosis. Developing therapies that can effectively target glioblastoma by crossing the BBB and evoke ferroptosis are, therefore, crucial for improving treatment outcomes. Herein, a versatile biomimetic nanoplatform, L-D-I/NPs, is designed that self-assembled by loading the antimalarial drug dihydroartemisinin (DHA) and the photosensitizer indocyanine green (ICG) onto lactoferrin (LF). This nanoplatform can selectively target glioblastoma by binding to low-density lipoprotein receptor-related protein-1 (LRP1) and crossing the BBB, thus inducing glioblastoma cell ferroptosis by boosting intracellular reactive oxygen species (ROS) accumulation and iron overload. In addition, L-D-I/NPs have demonstrated the ability to effectively suppress the progression of orthotopic glioblastoma and significantly prolong survival in a mouse glioblastoma model. This nanoplatform has facilitated the application of non-chemotherapeutic drugs in tumor treatment with minimal adverse effects, paving the way for highly efficient ferroptosis-based therapies for glioblastoma.


Subject(s)
Brain Neoplasms , Ferroptosis , Glioblastoma , Glioma , Mice , Animals , Glioblastoma/pathology , Drug Repositioning , Blood-Brain Barrier/metabolism , Glioma/metabolism , Brain Neoplasms/metabolism , Cell Line, Tumor
8.
Biomater Sci ; 11(14): 4948-4959, 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37314787

ABSTRACT

Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.


Subject(s)
Antineoplastic Agents , Nanoparticles , Urinary Bladder Neoplasms , Animals , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/metabolism , Urinary Bladder Neoplasms/pathology , Doxorubicin/therapeutic use , Urinary Bladder/metabolism , Administration, Intravesical
9.
Mater Horiz ; 10(8): 2927-2935, 2023 07 31.
Article in English | MEDLINE | ID: mdl-37158992

ABSTRACT

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.


Subject(s)
Nanoparticles , Nanostructures , Neoplasms , Animals , Mice , Nanostructures/therapeutic use , Neoplasms/therapy , Nanoparticles/therapeutic use , T-Lymphocytes, Cytotoxic , Immunity , Tumor Microenvironment
10.
Plant Physiol Biochem ; 197: 107627, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36940523

ABSTRACT

5-hydroxytryptamine (5-HT) is ubiquitously present in animals and plants, playing a vital regulatory role. SERT, a conserved serotonin reuptake transporter in animals, regulates intracellular and extracellular concentrations of 5-HT. Few studies have reported 5-HT transporters in plants. Hence, we cloned MmSERT, a serotonin reuptake transporter, from Mus musculus. Ectopic expression of MmSERT into apple calli, apple roots and Arabidopsis. Because 5-HT plays a momentous role in plant stress tolerance, we used MmSERT transgenic materials for stress treatment. We found that MmSERT transgenic materials, including apple calli, apple roots and Arabidopsis, exhibited a stronger salt tolerance phenotype. The reactive oxygen species (ROS) produced were significantly lower in MmSERT transgenic materials compared with controls under salt stress. Meanwhile, MmSERT induced the expression of SOS1, SOS3, NHX1, LEA5 and LTP1 in response to salt stress. 5-HT is the precursor of melatonin, which regulates plant growth under adversity and effectively scavenges ROS. Detection of MmSERT transgenic apple calli and Arabidopsis revealed higher melatonin levels than controls. Besides, MmSERT decreased the sensitivity of apple calli and Arabidopsis to abscisic acid (ABA). In summary, these results demonstrated that MmSERT plays a vital role in plant stress resistances, which perhaps serves as a reference for the application of transgenic technology to improve crops in the future.


Subject(s)
Arabidopsis , Malus , Melatonin , Animals , Mice , Abscisic Acid/metabolism , Arabidopsis/physiology , Salt Tolerance , Serotonin , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin Plasma Membrane Transport Proteins/pharmacology , Reactive Oxygen Species/metabolism , Ectopic Gene Expression , Melatonin/pharmacology , Plants, Genetically Modified/metabolism , Gene Expression Regulation, Plant , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
11.
Adv Mater ; 35(8): e2207686, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36502507

ABSTRACT

Obesity treatment is a global public health challenge due to inadequate weight loss and weight regain even after endeavors with multimodal treatments. Considering the abundance of resident macrophages in adipose tissues, precise regulation of the interactions between macrophages and adipocytes may provide chances for immunotherapy of obesity. Herein, inspired by the phagocytosis of macrophages to clear apoptotic cells in homeostasis, an immunotherapy strategy for obesity treatment is proposed for the first time through apoptotic camouflage of adipocytes by PA Au BPs to activate macrophages for clearance, where PA Au BPs are gold nanobipyramids engineered with adipose-targeting and apoptotic cell-mimicking functions. During clearance, the macrophage is switched from pro-inflammatory M1 to anti-inflammatory M2, remarkably modulating the immune microenvironment of adipose tissues to prevent weight regain. After inguinal injection with PA Au BPs, the body weights of obese mice are effectively decreased by 24.4% and can be decreased by 33.3% when combined with photothermal lipolysis, and little weight regain is associated with these treatments. This study demonstrates that the strategy of camouflaging adipocytes with apoptotic features holds great potential for obesity immunotherapy.


Subject(s)
Adipocytes , Adipose Tissue , Animals , Mice , Adipocytes/physiology , Obesity , Weight Gain , Immunotherapy , Mice, Inbred C57BL
12.
Small ; 19(2): e2205354, 2023 01.
Article in English | MEDLINE | ID: mdl-36399643

ABSTRACT

Durable glioblastoma multiforme (GBM) management requires long-term chemotherapy after surgery to eliminate remaining cancerous tissues. Among chemotherapeutics, temozolomide is considered as the first-line drug for GBM therapy, but the treatment outcome is not satisfactory. Notably, regorafenib, an oral multi-kinase inhibitor, has been reported to exert a markedly superior effect on GBM suppression compared with temozolomide. However, poor site-specific delivery and bioavailability significantly restrict the efficient permeability of regorafenib to brain lesions and compromise its treatment efficacy. Therefore, human H-ferritin (HFn), regorafenib, and Cu2+ are rationally designed as a brain-targeted nanoplatform (HFn-Cu-REGO NPs), fulfilling the task of site-specific delivery and manipulating autophagy and cuproptosis against GBM. Herein, HFn affords a preferential accumulation capacity to GBM due to transferrin receptor 1 (TfR1)-mediated active targeting and pH-responsive delivery behavior. Moreover, regorafenib can inhibit autophagosome-lysosome fusion, resulting in lethal autophagy arrest in GBM cells. Furthermore, Cu2+ not only facilitates the encapsulation of regorafenib to HFn through coordination interaction but also disturbs copper homeostasis for triggering cuproptosis, resulting in a synergistical effect with regorafenib-mediated lethal autophagy arrest against GBM. Therefore, this work may broaden the clinical application scope of Cu2+ and regorafenib in GBM treatment via modulating autophagy and cuproptosis.


Subject(s)
Apoptosis , Brain Neoplasms , Glioblastoma , Humans , Apoferritins , Autophagy , Brain , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cell Line, Tumor , Glioblastoma/drug therapy , Glioblastoma/pathology , Temozolomide/pharmacology , Temozolomide/therapeutic use , Copper
13.
Front Oncol ; 12: 1074307, 2022.
Article in English | MEDLINE | ID: mdl-36561529

ABSTRACT

N6-methyladenosinen (m6A) methylation is a frequent RNA methylation modification that is regulated by three proteins: "writers", "erasers", and "readers". The m6A modification regulates RNA stability and other mechanisms, including translation, cleavage, and degradation. Interestingly, recent research has linked m6A RNA modification to the occurrence and development of cancers, such as hepatocellular carcinoma and non-small cell lung cancer. This review summarizes the regulatory role of m6A RNA modification in gastric cancer (GC), including targets, the mechanisms of action, and the potential signaling pathways. Our present findings can facilitate our understanding of the significance of m6A RNA modification in GC.

14.
J Control Release ; 352: 766-775, 2022 12.
Article in English | MEDLINE | ID: mdl-36343763

ABSTRACT

Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemoresistance remaining a major obstacle in CRC treatment. Sodium persulfate (Na2S2O8) is a novel agent capable of producing •SO4- and Na+ for chemodynamic therapy (CDT). This can induce pyroptosis and ferroptosis instead of conventional apoptosis in tumor cells. Meanwhile, IR780-iodide (IR780), as an excellent phototherapy agent, can generate hyperthermia and generate a large amount of reactive oxygen species (ROS) to synergize with the CDT of Na2S2O8, with potential to overcome chemoresistance in CRC. However, the low stability of Na2S2O8 and the poor solubility of IR780 limit their applications in the medical field. Accordingly, for the first time, D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), Na2S2O8 and IR780 were rationally designed in a cascade-amplifying nanoplatform (Na2S2O8-IR780 NPs) via a co-assembly strategy. Combining Na2S2O8 and IR780 in a nanoplatform improves the stability of Na2S2O8 and the solubility of IR780. As a result, the Na2S2O8-IR780 NPs exhibited excellent antitumor efficacy in CRC cell lines and five chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. This photo-chemodynamic nanoplatform provides a brand-new paradigm by manipulating osmolarity and redox homeostasis to overcome chemo-resistance and holds great potential for the treatment of CRC.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Nanoparticles , Mice , Animals , Humans , Mice, Nude , Indoles , Phototherapy , Oxidation-Reduction , Osmolar Concentration , Homeostasis , Colorectal Neoplasms/drug therapy , Cell Line, Tumor
15.
Int J Mol Sci ; 23(18)2022 Sep 17.
Article in English | MEDLINE | ID: mdl-36142797

ABSTRACT

Strigolactones (SLs) are a class of important hormones in the regulation of plant branching. In the model plant Arabidopsis, AtMAX1 encodes a cytochrome P450 protein and is a crucial gene in the strigolactone synthesis pathway. Yet, the regulatory mechanism of MAX1 in the shoot branching of wintersweet (Chimonanthus praecox) remains unclear. Here we identified and isolated three MAX1 homologous genes, namely CpMAX1a, CpMAX1b, and CpMAX1c. Quantitative real-time PCR (qRT-PCR) revealed the expression of CpMAX1a in all tissues, being highest in leaves, whereas CpMAX1b was only expressed in stems, while CpMAX1c was expressed in both roots and stem tips. However, CpMAX1a's expression decreased significantly after decapitation; hence, we verified its gene function. CpMAX1a was located in Arabidopsis chloroplasts. Overexpressing CpMAX1a restored the phenotype of the branching mutant max1−3, and reduced the rosette branch number, but resulted in no significant phenotypic differences from the wild type. Additionally, expression of AtBRC1 was significantly upregulated in transgenic lines, indicating that the CpMAX1a gene has a function similar to the homologous gene of Arabidopsis. In conclusion, our study shows that CpMAX1a plays a conserved role in regulating the branch development of wintersweet. This work provides a molecular and theoretical basis for better understanding the branch development of wintersweet.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Calycanthaceae , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation, Plant , Hormones/metabolism , Lactones/metabolism , Plant Shoots/metabolism
16.
Adv Healthc Mater ; 11(19): e2200776, 2022 10.
Article in English | MEDLINE | ID: mdl-35912918

ABSTRACT

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.


Subject(s)
Neoplasms , Prodrugs , Anthraquinones , Humans , Immunologic Factors/pharmacology , Immunotherapy/methods , Iron/pharmacology , Macrophages , Neoplasms/drug therapy , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/pharmacology , Phototherapy , Polyethylene Glycols/pharmacology , Prodrugs/pharmacology , Tumor Microenvironment
17.
Int J Pharm ; 624: 122002, 2022 Aug 25.
Article in English | MEDLINE | ID: mdl-35817272

ABSTRACT

Tumor immunotherapy is a promising strategy to activate the immune system and eliminate tumors. Major histocompatibility complex I (MHC-I) is usually applied to potentiate antigen presentation, but it is associated with upregulation of programmed death ligand 1 (PD-L1) expression, which is unfavorable for activation of immune responses. Moreover, poor permeability of various therapeutic antibodies results in the limited immune response rates of most patients. It is necessary to develop combined small molecule drug delivery systems for simultaneous upregulation of MHC-I expression and downregulation of PD-L1 expression, promoting effective tumor treatment. A moderate dose of doxorubicin hydrochloride (DOX) can induce upregulation of MHC-I expression, while deferasirox (DFX) can inhibit the PI3K-Akt pathway, which potentially downregulates PD-L1 expression. In the present study, we designed a pH-sensitive liposome to incorporate DOX in the hydrophilic cavity and embed DFX in the hydrophobic shell, forming a dual delivery system (DOX-DFXL). In a B16F10 melanoma-bearing mouse model, DOX and DFX were released in acidic tumor microenvironment, which further lead to enhanced antigen presentation and infiltration of T cells into tumor tissues as a result of tumor remission. This codelivery system holds great potential for clinical applications of tumor immunotherapy.


Subject(s)
Melanoma , Nanoparticles , Animals , B7-H1 Antigen , Cell Line, Tumor , Deferasirox , Down-Regulation , Doxorubicin , Immunotherapy/methods , Liposomes , Major Histocompatibility Complex , Mice , Nanoparticles/chemistry , Phosphatidylinositol 3-Kinases , Tumor Microenvironment , Up-Regulation
18.
J Control Release ; 348: 590-600, 2022 08.
Article in English | MEDLINE | ID: mdl-35716882

ABSTRACT

Recently, lactate has been considered as an alternative direct energy substance to glucose for tumor proliferation and metastasis. Meanwhile, mitochondria, as important energy-supplying organelles, are also closely related to tumor progression. Consequently, a new research direction for lactate comprises lactate deprivation coupled with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis. Herein, linoleic acid-conjugated hyaluronic acid (HL), disulfide bond-rich nanovehicle (mesoporous silica, MOS), mitochondria-targeted IR780 (M780) and lactate oxidase (LOD) are rationally designed as a specific-targeting metabolism nanomodulator (HL/MOS@M780&LOD NPs), fulfilling the task of simultaneous depriving cells of lactate and damaging mitochondria to prevent tumor metastasis. Interestingly, M780-mediated photodynamic therapy (PDT) and LOD-mediated starvation therapy can effectively exacerbate the hypoxia state of tumor cells, thereby increasing the free iron levels to activate ferroptosis. On one hand, pyruvic acid and H2O2 generated by LOD-mediated lactate metabolism can provide powerful conditions for iron-catalyzed ferroptosis. On the other, the depleted GSH and increased reactive oxygen species (ROS) can oxidize linoleic acid into lipid peroxides (LPO) to further augment ferroptosis. The designed nanomodulator therefore shows great promise for fighting tumor metastasis by manipulating energy metabolism and the hypoxia microenvironment.


Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Cell Line, Tumor , Humans , Hydrogen Peroxide , Hypoxia , Iron , Lactates , Linoleic Acid , Neoplasms/drug therapy , Neoplasms/metabolism , Tumor Microenvironment
19.
Toxics ; 10(6)2022 May 24.
Article in English | MEDLINE | ID: mdl-35736885

ABSTRACT

Gold nanomaterials (Au NMs) have been widely used in cosmetic products for improving the brightening, and reducing the wrinkling of, skin, etc.; however, the dermal safety of Au NMs is rarely concerned. A previous study found that cosmetics could enhance the toxicity of Au nanosheets, but different physicochemical properties of Au NMs will induce different interaction modes with ingredients of cosmetics, potentially leading to different toxicity profiles. In the present study, spherical and rodlike Au NMs were first found in commercial cosmetics, and then Au nanospheres (NSs) with different sizes and Au nanorods (NRs) with different aspect ratios were prepared to simulate these Au NMs in cosmetics and further investigate their toxicity before and after embedment in cosmetics. It was found that the primary sizes, morphologies, and optical absorptions of these Au NSs and NRs before and after embedment were similar; however, their hydrodynamic sizes and zeta potentials were noticeably different. Then, these Au NSs and NRs presented weak or no cytotoxicity against HaCaT keratinocytes, while cosmetic cream could alleviate their cytotoxicity. Moreover, the cream could enhance the accumulation of Au NSs and NRs in the skin of hairless mice, but it also alleviated the toxicological responses of Au NSs and NRs in terms of superoxide dismutase (SOD) elevation and malondialdehyde (MDA) reduction. Therefore, the embedment of Au NSs and NRs into cosmetics can alleviate the in vitro and in vivo dermal toxicities of Au NSs and NRs.

20.
Mater Today Bio ; 15: 100289, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35634171

ABSTRACT

Previously used in anti-fungal therapy, itraconazole has now been shown to be successful in treating advanced breast cancer (NCT00798135). However, its poor solubility still restricts its application in clinical treatment. There is therefore an urgent need for combined methods to enhance the therapeutic effect of itraconazole (IC) in breast cancer treatment. With this goal, co-assembled IC/IR820 NPs with synergistic photonic hyperthermia and itraconazole payloads have been constructed to overcome these shortcomings. The IC/IR820 NPs show an enhanced therapeutic effect on breast cancer by inducing reactive oxygen species (ROS)-mediated apoptosis and autophagic death. Further evaluation in a mouse model has shown impressive effects of the IC/IR820 NPs on both inhibiting tumor metastasis and activating immunity to prevent tumor recurrence. Mechanistically, itraconazole may promote both tumor cell antigen presentation through autophagy and the activation of dendritic cells to induce an immune response, which displays a synergistic effect with the immune response generated by photothermal therapy to inhibit tumor recurrence. This strategy of combining itraconazole and IR820 into one minimalist and robust nanoplatform through co-assembly results in excellent therapeutic efficacy, suggesting its potential application as an alternative method for the clinical treatment of breast cancer.

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