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1.
J Control Release ; 320: 159-167, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978443

RESUMO

Glucose-responsive insulin delivery system mimicking the function of pancreatic ß-cells to maintain blood glucose homeostasis would effectively alleviate diabetes. Here, a new glucose-responsive delivery (ZIF@Ins&GOx) for self-regulated insulin release was constructed by encapsulating insulin and glucose oxidase (GOx) into pH-sensitive zeolitic imidazole framework-8 (ZIF-8) nanocrystals. After entering the cavities of ZIF-8, glucose can be oxidized into gluconic acid by GOx, causing a decrease in local pH. Then, ZIF-8 nanocrystals would be degraded under the acidic microenvironment that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies indicated that the biological activity of insulin could be protected by the rigid structure of ZIF-8 and the release of insulin could be modulated in response to glucose concentrations. In vivo experiments demonstrated that a single subcutaneous injection of the ZIF@Ins&GOx would facilitate the stabilization of blood glucose level of normoglycemic state for up to 72 h in type 1 diabetes (T1D). The multifunctional insulin delivery system shows a new proof-of-concept for T1D treatment by using ZIF-8 nanocrystals loaded with insulin and enzyme.

2.
Biomaterials ; 223: 119472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31499254

RESUMO

Inflammation during photothermal therapy (PTT) of tumor usually results in adverse consequences. Here, a biomembrane camouflaged nanomedicine (mPDAB) containing polydopamine and ammonia borane was designed to enhance PTT efficacy and mitigate inflammation. Polydopamine, a biocompatible photothermal agent, can effectively convert light into heat for PTT. Ammonia borane was linked to the surface of polydopamine through the interaction of hydrogen bonding, which could destroy redox homoeostasis in tumor cells and reduce inflammation by H2 release in tumor microenvironment. Owing to the same origin of outer biomembranes, mPDAB showed excellent tumor accumulation and low systemic toxicity in a breast tumor model. Excellent PTT efficacy and inflammation reduction made the mPDAB completely eliminate the primary tumors, while also restraining the outgrowth of distant dormant tumors. The biomimetic nanomedicine shows potentials as a universal inflammation-self-alleviated platform to ameliorate inflammation-related disease treatment, including but not limited to PTT for tumor.

3.
Nat Commun ; 10(1): 3199, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324770

RESUMO

Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.


Assuntos
Apresentação do Antígeno/imunologia , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Membrana Celular/imunologia , Nanopartículas/uso terapêutico , Animais , Fusão Celular , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Feminino , Imunoterapia , Ativação Linfocitária , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia , Transcriptoma , Transplante Heterólogo
4.
Adv Mater ; 31(18): e1900499, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30907473

RESUMO

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.


Assuntos
Membrana Celular/química , Células Dendríticas/citologia , Imunoterapia , Nanoestruturas/química , Animais , Anticorpos/química , Anticorpos/imunologia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Receptores de Hialuronatos/imunologia , Estruturas Metalorgânicas/química , Camundongos , Camundongos Nus , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/uso terapêutico , Transplante Heterólogo , Zircônio/química
5.
Biomaterials ; 194: 84-93, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30583151

RESUMO

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)32+) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C3N4) for the first time. While exposured to two-photon laser, Ru(bpy)32+ was activated to generate singlet oxygen (1O2) and Fe-C3N4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy)32+ to Fe-C3N4, O2 generation by Fe-C3N4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating 1O2 generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.

6.
Adv Mater ; 30(35): e1802006, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30015997

RESUMO

Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in mammals, an aggressive man-made RBC (AmmRBC) is created to combat the hypoxia-mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme-mimicking polydopamine, and polydopamine-carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen-carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man-made pseudo-RBC shows potentials as a universal oxygen-self-supplied platform to sensitize hypoxia-limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.


Assuntos
Eritrócitos , Animais , Hipóxia Celular , Oxigênio , Fotoquimioterapia , Fármacos Fotossensibilizantes
7.
Adv Mater ; 30(22): e1707459, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29675900

RESUMO

Many viruses have a lipid envelope derived from the host cell membrane that contributes much to the host specificity and the cellular invasion. This study puts forward a virus-inspired technology that allows targeted genetic delivery free from man-made materials. Genetic therapeutics, metal ions, and biologically derived cell membranes are nanointegrated. Vulnerable genetic therapeutics contained in the formed "nanogene" can be well protected from unwanted attacks by blood components and enzymes. The surface envelope composed of cancer cell membrane fragments enables host-specific targeting of the nanogene to the source cancer cells and homologous tumors while effectively inhibiting recognition by macrophages. High transfection efficiency highlights the potential of this technology for practical applications. Another unique merit of this technology arises from the facile combination of special biofunction of metal ions with genetic therapy. Typically, Gd(III)-involved nanogene generates a much higher T1 relaxation rate than the clinically used Gd magnetic resonance imaging agent and harvests the enhanced MRI contrast at tumors. This virus-inspired technology points out a distinctive new avenue for the disease-specific transport of genetic therapeutics and other biomacromolecules.

8.
Nano Lett ; 16(9): 5895-901, 2016 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-27513184

RESUMO

The ultimate goal in cancer therapy and diagnosis is to achieve highly specific targeting to cancer cells. Coated with the source cancer cell membrane specifically derived from the homologous tumors, the nanoparticles are identified with the self-recognition internalization by the source cancer cell lines in vitro and the highly tumor-selective targeting "homing" to the homologous tumor in vivo even in the competition of another heterologous tumor. As the result, MNP@DOX@CCCM nanovehicle showed strong potency for tumor treatment in vivo and the MR imaging. This bioinspired strategy shows great potential for precise therapy/diagnosis of various tumors merely by adjusting the cell membrane source accordingly on the nanoparticle surface.


Assuntos
Membrana Celular/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Compostos Férricos/química , Humanos , Imagem por Ressonância Magnética , Magnetismo , Camundongos , Neoplasias/tratamento farmacológico
9.
ACS Appl Mater Interfaces ; 8(11): 6784-9, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-26962876

RESUMO

It is challenging but imperative to merge together specific inorganic nanomaterials with macromolecular and small-molecule therapeutics into one nanoentity for all-in-one theranostic/remedy. We establish a versatile nanotechnology to nanoentrap magnetic nanoparticles, doxorubicin, and DNA, thus allowing the combination of magnetic targeting, magnetic resonance (MR) imaging, gene transport, and bioresponsive chemotherapy. We hope this nanotechnology can prompt the development of complex inorganic/organic nanosystems for various applications.


Assuntos
Meios de Contraste , Sistemas de Liberação de Medicamentos/métodos , Técnicas de Transferência de Genes , Campos Magnéticos , Imagem por Ressonância Magnética/métodos , Nanopartículas , Animais , Meios de Contraste/química , Meios de Contraste/farmacologia , DNA/química , DNA/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Células HeLa , Humanos , Camundongos , Nanopartículas/química
10.
J Psychiatry Neurosci ; 33(3): 244-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18592039

RESUMO

OBJECTIVE: Telomere shortening has been observed in many human diseases, including atherosclerosis, cancer, aging syndromes, Alzheimer disease and vascular dementia. The present study aimed to investigate the mean telomere lengths of patients with schizophrenia. METHODS: We analyzed the lengths of telomeric DNA, comparing 2 groups of patients with schizophrenia (34 good responders and 34 poor responders). A control group of 76 healthy volunteers was also included. Blood samples were obtained, and telomere length was measured by Southern blot analysis on the mean length of terminal restriction fragment (TRF). RESULTS: Compared with the control group, a significant amount of telomere shortening was found in peripheral blood leukocytes from patients with schizophrenia who experienced poor response to antipsychotics (p < 0.001). CONCLUSION: Shortened telomere length in chronic schizophrenia may be a trait marker caused by oxidative stress, and the ensuing cellular dysfunction may be a factor contributing to the progressive deterioration in treatment-resistant schizophrenia.


Assuntos
Resistência a Medicamentos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Telômero/metabolismo , Adulto , Southern Blotting , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Biol Psychiatry ; 51(11): 896-901, 2002 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-12022963

RESUMO

BACKGROUND: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The human serotonin receptor 1B, encoded by the HTR1B gene, is a presynaptic serotonin autoreceptor that plays a role in regulating serotonin synthesis and release. Because the linkage of antisocial alcoholism to the HTR1B gene was recently reported in two populations, it was of interest to identify genetic variants at the HTR1B locus and study their association with alcoholism in the Taiwanese Han population. METHODS: We sequenced DNA from Taiwanese Han to screen for genetic variation in the coding, promoter, and partial 3' untranslated regions of the HTR1B locus of 158 alcohol-dependent cases with withdrawal symptoms and 149 control subjects, who either never drank or drank only occasionally and in low quantities. RESULTS: Seven variants were identified. Positive associations were found between variant A-161T and alcohol dependence at both the allelic and genotypic level. In addition, an expression study showed that the A-161T variant affected reporter gene activity. CONCLUSIONS: Our results support an association between HTR1B and alcohol dependence. The HTR1B A-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B.


Assuntos
Alcoolismo/genética , Receptores de Serotonina/genética , Alcoolismo/metabolismo , Alelos , Feminino , Genótipo , Humanos , Masculino , Polimorfismo Genético , Receptor 5-HT1B de Serotonina , Taiwan , Transcrição Genética
12.
Compr Psychiatry ; 43(2): 158-66, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11893995

RESUMO

Despite the wide use of the Tridimensional Personality Questionnaire (TPQ) in Western populations as a useful tool integrating both genetic and environmental influences on personality, some of its constructs remain questionable. In this study, we examined the psychometric properties of the TPQ and its relationship with aggression in Taiwanese adults. The subjects were 201 Taiwanese adults of wide ranges in age and educational level. Subjects were assessed using a Chinese version of the TPQ and the Brown-Goodwin Aggression Inventory. The internal consistency of the Chinese version of the TPQ scales is found to be mostly in the acceptable range except for the reward dependence (RD) scale and its subscales. The results of factor analysis of the 12 TPQ subscales partially support the four-factor model rather than the original three-factor model. The construct validity of the novelty seeking (NS) and harm avoidance (HA) dimensions is supported by the findings that the NS is negatively correlated with age, the NS1 subscale is slightly negatively correlated with all the HA subscales, and the NS is positively correlated with aggression. We conclude that both the HA and NS scales of the TPQ are cross-culturally robust, while the RD scale needs to be refined.


Assuntos
Transtornos da Personalidade/diagnóstico , Inventário de Personalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/epidemiologia , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Taiwan/epidemiologia
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