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1.
Neurosci Lett ; 836: 137861, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849102

ABSTRACT

The continued influence effect of misinformation (CIEM) can negatively affect individuals' reasoning and judgment processes. This research aims to enhance the correction of misinformation and foster rational judgement by investigating the internal brain mechanisms involved in the processing of the CIEM through the use of task-based functional magnetic resonance imaging combined with Granger causality analysis. Our findings demonstrate notable effective interactions in varying directions between the left inferior frontal gyrus and middle temporal gyrus during the encoding phase, and between the right anterior cingulate gyrus and left inferior occipital gyrus in the retrieval phase. These insights elucidate the roles of mental model updating and retrieval failure in the processing of CIEM, offering more granular evidence to support the differentiation in processing phases.

2.
Nano Lett ; 24(15): 4691-4701, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38588212

ABSTRACT

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.


Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Immunotherapy , Radioimmunotherapy , Glucose , Glucose Oxidase , Immunosuppressive Agents , Lactic Acid , Neoplasms/therapy , Cell Line, Tumor
3.
Angew Chem Int Ed Engl ; 63(13): e202318539, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38303647

ABSTRACT

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)-based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade-off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone-lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs-based two-component nanoplatform consisting of prodrug-loaded AuNPs-ImLND and tumor-targeting peptide RGD-conjugated AuNPs-DBCO-RGD is designed. In the therapeutic regimen, AuNPs-DBCO-RGD are intravenously injected first for tumor-specific enrichment and retention. Once the arrival of AuNPs-ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT.


Subject(s)
Indazoles , Metal Nanoparticles , Nanoparticles , Neoplasms , Prodrugs , Humans , Gold , Photothermal Therapy , Metal Nanoparticles/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathology , Prodrugs/therapeutic use , Oligopeptides/therapeutic use , Cell Line, Tumor
4.
Adv Mater ; 36(6): e2309094, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38014890

ABSTRACT

Inhibition of glutamine metabolism in tumor cells can cause metabolic compensation-mediated glycolysis enhancement and PD-L1 upregulation-induced immune evasion, significantly limiting the therapeutic efficacy of glutamine inhibitors. Here, inspired by the specific binding of receptor and ligand, a PD-L1-targeting metabolism and immune regulator (PMIR) are constructed by decorating the glutaminase inhibitor (BPTES)-loading zeolitic imidazolate framework (ZIF) with PD-L1-targeting peptides for regulating the metabolism within the tumor microenvironment (TME) to improve immunotherapy. At tumor sites, PMIR inhibits glutamine metabolism of tumor cells for elevating glutamine levels within the TME to improve the function of immune cells. Ingeniously, the accompanying PD-L1 upregulation on tumor cells causes self-amplifying accumulation of PMIR through PD-L1 targeting, while also blocking PD-L1, which has the effects of converting enemies into friends. Meanwhile, PMIR exactly offsets the compensatory glycolysis, while disrupting the redox homeostasis in tumor cells via the cooperation of components of the ZIF and BPTES. These together cause immunogenic cell death of tumor cells and relieve PD-L1-mediated immune evasion, further reshaping the immunosuppressive TME and evoking robust immune responses to effectively suppress bilateral tumor progression and metastasis. This work proposes a rational strategy to surmount the obstacles in glutamine inhibition for boosting existing clinical treatments.


Subject(s)
B7-H1 Antigen , Glutamine , Humans , B7-H1 Antigen/metabolism , Cell Line, Tumor , Glutamine/antagonists & inhibitors , Glutamine/metabolism , Immunosuppressive Agents , Immunotherapy , Metabolic Reprogramming , Tumor Microenvironment
5.
ACS Nano ; 17(24): 24947-24960, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38055727

ABSTRACT

Cancer vaccines have been considered to be an alternative therapeutic strategy for tumor therapy in the past decade. However, the popularity and efficacy of cancer vaccines were hampered by tumor antigen heterogeneity and the impaired function of cross-presentation in the tumor-infiltrating dendritic cells (TIDCs). To overcome these challenges, we engineered an in situ nanovaccine (named as TPOP) based on lipid metabolism-regulating and innate immune-stimulated nanoparticles. TPOP could capture tumor antigens and induce specific recognition by TIDCs to be taken up. Meanwhile, TPOP could manipulate TIDC lipid metabolism and inhibit de novo synthesis of fatty acids, thus improving the ability of TIDCs to cross-present by reducing their lipid accumulation. Significantly, intratumoral injection of TPOP combined with pretreatment with doxorubicin showed a considerable therapeutic effect in the subcutaneous mouse colorectal cancer model and melanoma model. Moreover, in combination with immune checkpoint inhibitors, such TPOP could markedly inhibit the growth of distant tumors by systemic antitumor immune responses. This work provides a safe and promising strategy for improving the function of immune cells by manipulating their metabolism and activating the immune system effectively for in situ cancer vaccines.


Subject(s)
Cancer Vaccines , Melanoma , Nanoparticles , Neoplasms , Mice , Animals , Nanovaccines , Dendritic Cells , Lipid Metabolism , Immunotherapy , Neoplasms/drug therapy , Melanoma/drug therapy , Antigens, Neoplasm/metabolism , Disease Models, Animal
6.
Org Lett ; 25(45): 8083-8088, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37922494

ABSTRACT

Rhodium(II) catalyzes carbene transfer from trimethylsilyldiazomethane to arylmethyl thioethers, generating sulfonium ylides that undergo [2,3]-sigmatropic rearrangement, punching quaternary centers into aromatic rings. The reaction works well with naphthalene, indole, and benzofuran ring systems, but the reaction is unsuccessful with the monocyclic benzene homologue. For aryl thioethers, Rh2(OAc)4 gives good results. For alkyl thioethers, the yields improve with Rh2(cap)4. Surprisingly, thioesters and thiocarbamates are also competent substrates for the reaction.

7.
Eur J Psychotraumatol ; 14(2): 2258723, 2023.
Article in English | MEDLINE | ID: mdl-37736668

ABSTRACT

Background: Childhood emotional neglect (CEN) confers a great risk for developing multiple psychiatric disorders; however, the neural basis for this association remains unknown. Using a dynamic functional connectivity approach, this study aimed to examine the effects of CEN experience on functional brain networks in young adults.Method: In total, 21 healthy young adults with CEN experience and 26 without childhood trauma experience were recruited. The childhood trauma experience was assessed using the childhood trauma questionnaire (CTQ), and eligible participants underwent resting-state functional MRI. Sliding windows and k-means clustering were used to identify temporal features of large-scale functional connectivity states (frequency, mean dwell time, and transition numbers).Result: Dynamic analysis revealed two separate connection states: state 1 was more frequent and characterized by extensive weak connections between the brain regions. State 2 was relatively infrequent and characterized by extensive strong connections between the brain regions. Compared to the control group, the CEN group had a longer mean dwell time in state 1 and significantly decreased transition numbers between states 1 and 2.Conclusion: The CEN experience affects the temporal properties of young adults' functional brain connectivity. Young adults with CEN experience tend to be stable in state 1 (extensive weak connections between the brain regions), reducing transitions between states, and reflecting impaired metastability or functional network flexibility.


We focus solely on the childhood emotional neglect experience and its long-term effects on brain function.Eligible participants with and without childhood emotional neglect were identified through a large-scale screen among young adults.The results found childhood emotional neglect experiences have a long-term impact on brain flexibility.


Subject(s)
Adverse Childhood Experiences , Mental Disorders , Young Adult , Humans , Brain/diagnostic imaging , Health Status
8.
ACS Nano ; 17(17): 17217-17232, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37584451

ABSTRACT

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.


Subject(s)
Adjuvants, Immunologic , Neoplasms , Humans , Adjuvants, Immunologic/pharmacology , Tumor Microenvironment , CD8-Positive T-Lymphocytes , Hydrogels/pharmacology , Macrophages , Neoplasms/therapy , Neoplasms/pathology , Phagocytosis , CD47 Antigen , Immunotherapy
9.
Mater Horiz ; 10(10): 4365-4379, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37455643

ABSTRACT

Tertiary lymphoid structures (TLSs) primarily constructed by multiple immune cells can effectively enhance tumor immune responses, but expediting the formation of TLSs is still an enormous challenge. Herein, a stimulator of interferon gene (STING)-activating hydrogel (ZCCG) was elaborately developed by coordinating Zn2+ with 4,5-imidazole dicarboxylic acid, and simultaneously integrating chitosan (a stimulant of STING pathway activation) and CpG (an agonist of toll-like receptor 9, TLR9) for initiating and activating cGAS-STING and TLR9 pathway-mediated immunotherapy. Moreover, the dual-pathway activation could effectively enhance the infiltration of immune cells and the expression of lymphocyte-recruiting chemokines in the tumor microenvironment (TME), thereby promoting the formation of TLSs and further strengthening tumoricidal immunity. Local administration of the hydrogel could prime systemic immune responses and long-term immune memory and improve the therapeutic effects of programmed death-1 antibody (αPD-1) to inhibit tumor progression, metastasis and recurrence. The engineered hydrogel lays the foundation for tumor immunotherapy strategies based on the enhanced formation of TLSs via the activation of the cGAS-STING and TLR9 pathways.


Subject(s)
Hydrogels , Tertiary Lymphoid Structures , Humans , Toll-Like Receptor 9 , Immunotherapy , Metals , Nucleotidyltransferases
10.
Adv Healthc Mater ; 12(23): e2300323, 2023 09.
Article in English | MEDLINE | ID: mdl-37212324

ABSTRACT

Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy.


Subject(s)
Cancer Vaccines , Nanoparticles , Neoplasms , Humans , Neoplasms/therapy , T-Lymphocytes, Cytotoxic , Immunotherapy , Antigens, Neoplasm , Tumor Microenvironment
11.
Sci Bull (Beijing) ; 68(6): 622-636, 2023 03 30.
Article in English | MEDLINE | ID: mdl-36914548

ABSTRACT

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. Herein, a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as HBMn-FA) was elaborately developed for activating and boosting STING-based immunotherapy. On the one hand, the high-levels of reactive oxygen species (ROS) in tumor cells induced by HBMn-FA-mediated ferroptosis elicited mitochondrial stress to cause the release of endogenous signaling mtDNA, which specifically initiate cGAS-STING pathway with the cooperation of Mn2+. On the other hand, the tumor-derived cytosolic double-stranded DNA (dsDNA) from debris of death cells caused by HBMn-FA further activated the cGAS-STING pathway in antigen-presenting cells (e.g., DCs). This bridging of ferroptosis and cGAS-STING pathway could expeditiously prime systemic antitumor immunity and enhance the therapeutic efficacy of checkpoint blockade to suppress tumor growth in both localized and metastatic tumor models. The designed nanotherapeutic platform paves the way for novel tumor immunotherapy strategies that are based on specific activation of STING pathway.


Subject(s)
Ferroptosis , Interferon Type I , Neoplasms , Humans , DNA, Mitochondrial , Immunotherapy , Interferon Type I/metabolism , Neoplasms/therapy , Nucleotidyltransferases/genetics
12.
Front Behav Neurosci ; 17: 927389, 2023.
Article in English | MEDLINE | ID: mdl-36969801

ABSTRACT

Childhood emotional neglect (CEN) has a relatively high incidence rate and substantially adverse effects. Many studies have found that CEN is closely related to emotion regulation and depression symptoms. Besides, the functional activity of the prefrontal lobe may also be related to them. However, the relationships between the above variables have not been thoroughly studied. This study recruited two groups of college students, namely, those with primary CEN (neglect group) and those without childhood trauma (control group), to explore the relationships among CEN, adulthood emotion regulation, depressive symptoms, and prefrontal resting functional connections. The methods used in this study included the Childhood Trauma Questionnaire (CTQ), Emotion Regulation Questionnaire (ERQ), Beck Depression Inventory-II (BDI-II) and resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared with the control group, the neglect group utilized the reappraisal strategy less frequently and displayed more depressive symptoms. The prefrontal functional connections with other brain regions in the neglect group were more robust than those in the control group using less stringent multiple correction standards. Across the two groups, the functional connection strength between the right orbitofrontal gyrus and the right middle frontal gyrus significantly negatively correlated with the ERQ reappraisal score and positively correlated with the BDI-II total score; the ERQ reappraisal score wholly mediated the relationship between the functional connection strength and the BDI-II total score. It suggests that primary CEN may closely correlate with more depressive symptoms in adulthood. Furthermore, the more robust spontaneous activity of the prefrontal lobe may also be closely associated with more depressive symptoms by utilizing a reappraisal strategy less frequently.

13.
Pathol Oncol Res ; 29: 1610819, 2023.
Article in English | MEDLINE | ID: mdl-36816541

ABSTRACT

The outcomes of patients with diffuse large B-cell lymphoma (DLBCL) vary widely, and about 40% of them could not be cured by the standard first-line treatment, R-CHOP, which could be due to the high heterogeneity of DLBCL. Here, we aim to construct a prognostic model based on the genetic signature of metabolic heterogeneity of DLBCL to explore therapeutic strategies for DLBCL patients. Clinical and transcriptomic data of one training and four validation cohorts of DLBCL were obtained from the GEO database. Metabolic subtypes were identified by PAM clustering of 1,916 metabolic genes in the 7 major metabolic pathways in the training cohort. DEGs among the metabolic clusters were then analyzed. In total, 108 prognosis-related DEGs were identified. Through univariable Cox and LASSO regression analyses, 15 DEGs were used to construct a risk score model. The overall survival (OS) and progression-free survival (PFS) of patients with high risk were significantly worse than those with low risk (OS: HR 2.86, 95%CI 2.04-4.01, p < 0.001; PFS: HR 2.42, 95% CI 1.77-3.31, p < 0.001). This model was also associated with OS in the four independent validation datasets (GSE10846: HR 1.65, p = 0.002; GSE53786: HR 2.05, p = 0.02; GSE87371: HR 1.85, p = 0.027; GSE23051: HR 6.16, p = 0.007) and PFS in the two validation datasets (GSE87371: HR 1.67, p = 0.033; GSE23051: HR 2.74, p = 0.049). Multivariable Cox analysis showed that in all datasets, the risk model could predict OS independent of clinical prognosis factors (p < 0.05). Compared with the high-risk group, patients in the low-risk group predictively respond to R-CHOP (p = 0.0042), PI3K inhibitor (p < 0.05), and proteasome inhibitor (p < 0.05). Therefore, in this study, we developed a signature model of 15 DEGs among 3 metabolic subtypes, which could predict survival and drug sensitivity in DLBCL patients.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Phosphatidylinositol 3-Kinases , Humans , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Vincristine/therapeutic use , Prednisone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
14.
Cancer Invest ; : 1-13, 2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36629468

ABSTRACT

The prognosis of acute myeloid leukemia (AML) is disappointing in most subtypes and varies widely. DNA damage response (DDR) is associated with prognosis and immunotherapy in multiple cancers. Here, we identify a signature of eight DDR-related genes associated with overall survival, which stratifies AML patients into high- and low-risk groups. Patients in low-risk group were more likely to respond to sorafenib. The signature could be an independent prognostic predictor for patients treated with ADE and ADE plus gemtuzumab ozogamicin. Therefore, this DDR prognostic signature might be applied to prognostic stratification and treatment selection in AML patients, which warrants further studies.

15.
Acta Psychol (Amst) ; 232: 103814, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36527819

ABSTRACT

Childhood emotional neglect (CEN) refers to a failure to meet the basic emotional needs of a child, which can seriously impact interpersonal communication and psychological health in young adults. Emotional face processing is critical in interpersonal communication; however, whether CEN affects this processing in young adults has not been investigated. Therefore, the current study aimed to explore the effects of CEN on emotional face processing in young adults. Using the Child Trauma Questionnaire, an online survey was conducted with 5010 students from four universities in Tianjin, China. After online interviews and diagnosis by professional doctors, we obtained 20 participants with CEN (CEN group) and 20 without CEN (control group). None of the participants had any mental diseases. A 2 × 4 mixed design was used to investigate the differences in accuracy and response time when identifying the valence of the emotional faces. Compared to the control group, the CEN group identified the valence of all emotional faces more slowly, but there was no significant difference between the two groups in terms of accuracy. CEN caused delayed emotional face processing in young adults, which may be related to unresponsive, unavailable, and limited emotional interaction patterns between parents and their children.


Subject(s)
Child Abuse , Facial Recognition , Mental Disorders , Child , Humans , Young Adult , Child Abuse/psychology , Emotions/physiology , Surveys and Questionnaires
16.
J Mater Chem B ; 9(45): 9333-9346, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34723316

ABSTRACT

Recently, nanomaterials have been well-studied in cancer therapy, but some of them often experience difficulties with degradation in vivo, which could cause severe damage to the human body. Among numerous biodegradable nanomaterials, antimonene nanosheets (AMNSs) are versatile, and possess photothermal and photodynamic properties and photoacoustic imaging (PAI) and drug loading ability. Herein, we employed a clearable multifunctional system. The small molecule photosensitizer IR820 and the gold nanoparticles (AuNPs) at small sizes of approximately 5 nm were loaded onto AMNSs coated with biodegradable chitosan (CS). This nanoplatform showed excellent photothermal and photodynamic properties, satisfactory degradability and photoacoustic imaging ability, good biocompatibility and effective NIR light triggered intracellular synergistic treatment. It also displayed good fluorescence imaging ability in the experiment of cell uptake. These suggested that this versatile nanoplatform was able to significantly enhance the therapeutic efficiency based on synergistic phototherapy, and could also be applied in fluorescence and photoacoustic dual imaging for integrating diagnosis and treatment.


Subject(s)
Antimony/chemistry , Nanostructures/chemistry , Phototherapy/methods , Biological Transport , HeLa Cells , Humans , Indocyanine Green/analogs & derivatives , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Reactive Oxygen Species
17.
J Colloid Interface Sci ; 601: 714-726, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34091318

ABSTRACT

Nanomaterials have shown great potential in cancer therapy, but the phenomenon of poor tumor recognition without cellular organelle accumulation usually leads to reduced therapeutic effects and enhanced side effects. Herein, we resolved this issue by employing a multifunctional peptide coating mainly composed of, from the inside out, a mitochondrial targeting segment, a cathepsin B-responsive segment and a zwitterionic antifouling segment. Then gold nanorods were modified with a peptide via ligand exchange, displaying excellent photothermal property and superior stability both before and after enzyme treatment. The in vitro and in vivo results showed that this nanoplatform possessed good biocompatibility, satisfactory mitochondria targeting ability, prolonged blood circulation lifetime and enhanced cellular uptake in tumors. This nanoplatform promoted effective near-infrared light-triggered subcellular hyperthermia treatment in vitro and exhibited excellent tumor ablation ability in vivo. These findings suggested that this multifunctional nanoplatform could significantly enhance the therapeutic efficiency of photothermal therapy based on activated mitochondrial targeting.


Subject(s)
Hyperthermia, Induced , Nanotubes , Neoplasms , Cathepsin B , Cell Line, Tumor , Gold , Humans , Mitochondria , Neoplasms/drug therapy , Peptides , Phototherapy
18.
J Biomater Appl ; 36(4): 565-578, 2021 10.
Article in English | MEDLINE | ID: mdl-33487068

ABSTRACT

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and in vitro antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.


Subject(s)
Drug Delivery Systems/methods , Drug Therapy/methods , Fluorouracil/pharmacology , Nanogels/chemistry , Photochemotherapy/methods , Phototherapy/methods , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Cell Line, Tumor , Humans , Hyperthermia, Induced/methods , Indocyanine Green , Nanogels/administration & dosage , Nanoparticles , Photosensitizing Agents , Polyethylene Glycols/administration & dosage , Polyethyleneimine/administration & dosage , Polymers , Temperature
19.
Front Psychol ; 11: 531147, 2020.
Article in English | MEDLINE | ID: mdl-33281654

ABSTRACT

Regulatory focus theory uses two different motivation focus systems-promotional and preventive-to describe how individuals approach positive goals and avoid negative goals. Moreover, the regulatory focus can manifest as chronic personality characteristics and can be situationally induced by tasks or the environment. The current study employed eye-tracking methodology to investigate how individuals who differ in their chronic regulatory focus (promotional vs. preventive) process information (Experiment 1) and whether an induced experimental situation could modulate features of their information processing (Experiment 2). Both experiments used a 3 × 3 grid information-processing task, containing eight information cells and a fixation cell; half the information cells were characterized by attribute-based information, and the other half by alternative-based information. We asked the subjects to view the grid based on their personal preferences and choose one of the virtual products presented in this grid to "purchase" by the end of each trial. Results of Experiment 1 show that promotional individuals do not exhibit a clear preference between the two types of information, whereas preventive individuals tend to fixate longer on the alternative-based information. In Experiment 2, we induced the situational regulatory focus via experimental tasks before the information-processing task. The results demonstrate that the behavioral motivation is significantly enhanced, thereby increasing the depth of the preferred mode of information processing, when the chronic regulatory focus matches the situational focus. In contrast, individuals process information more thoroughly, using both processing modes, in the non-fit condition, i.e., when the focuses do not match.

20.
Inorg Chem ; 59(23): 17276-17281, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33231077

ABSTRACT

A biocompatible Y(III)-based metal-organic framework [Y4(TATB)2]·(DMF)3.5·(H2O) (ZJU-16, H3TATB= 4,4',4''-(1,3,5-triazine-2,4,6-triyl) tribenzoic acid) was synthesized, and it was adopted to load Mn2+ for chemodynamic therapy. Meanwhile, ibuprofen sodium (IBUNa), an anti-inflammatory drug, was introduced to increase the amount of Mn2+ (about 5.66 wt %) due to the low loading capacity of Mn2+. Mn&IBUNa@ZJU-16 which was loaded by Mn2+ and IBUNa exhibited significant effects of chemodynamic therapy and excellent inhibition of the 4T1 tumor cell growth, implying its long-term prospects in chemodynamic therapy and its possibility in bimodal cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Biocompatible Materials/pharmacology , Breast Neoplasms/drug therapy , Metal-Organic Frameworks/pharmacology , Yttrium/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Drug Liberation , Drug Screening Assays, Antitumor , Female , Metal-Organic Frameworks/chemical synthesis , Metal-Organic Frameworks/chemistry , Mice , Tumor Cells, Cultured , Yttrium/chemistry
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