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1.
Immunity ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38889716

RESUMO

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

2.
J Am Chem Soc ; 146(17): 11679-11693, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38482849

RESUMO

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.


Assuntos
Vacinas Anticâncer , Lipídeos , Lipossomos , Nanopartículas , RNA Mensageiro , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Nanopartículas/química , Animais , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Lipídeos/química , Humanos , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Polímeros/química , Guanidinas/química , Guanidinas/farmacologia , Linhagem Celular Tumoral
3.
Chem Soc Rev ; 52(9): 2911-2945, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36987988

RESUMO

Vital biomacromolecules, such as RNA, DNA, polysaccharides and proteins, are synthesized inside cells via the polymerization of small biomolecules to support and multiply life. The study of polymerization reactions in living organisms is an emerging field in which the high diversity and efficiency of chemistry as well as the flexibility and ingeniousness of physiological environment are incisively and vividly embodied. Efforts have been made to design and develop in situ intra/extracellular polymerization reactions. Many important research areas, including cell surface engineering, biocompatible polymerization, cell behavior regulation, living cell imaging, targeted bacteriostasis and precise tumor therapy, have witnessed the elegant demeanour of polymerization reactions in living organisms. In this review, recent advances in polymerization in living organisms are summarized and presented according to different polymerization methods. The inspiration from biomacromolecule synthesis in nature highlights the feasibility and uniqueness of triggering living polymerization for cell-based biological applications. A series of examples of polymerization reactions in living organisms are discussed, along with their designs, mechanisms of action, and corresponding applications. The current challenges and prospects in this lifeful field are also proposed.


Assuntos
DNA , Proteínas , Polimerização , DNA/química , Tiram
4.
Angew Chem Int Ed Engl ; 63(13): e202318515, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38320193

RESUMO

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.


Assuntos
Vacinas Anticâncer , Lipossomos , Nanopartículas , Neoplasias , Humanos , Apresentação de Antígeno , Vacinas de mRNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo
5.
J Am Chem Soc ; 145(34): 18789-18799, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37535445

RESUMO

Despite the tremendous breakthrough of immunotherapy, the low response rate and resistance of immune checkpoint inhibitors (ICIs) toward solid tumors occur frequently. A highly hypoxic tumor microenvironment (TME) provides tumor cells with high concentrations of HIF-1α and polyamines to evade immune cell destruction. Reprogramming of an immunogenic TME has exhibited a brilliant future to boost immunotherapeutic performances. Herein, a supramolecular nanomedicine (TAPP) is developed on the basis of host-guest molecular recognition and metal coordination, showing the capability to remodel the immunosuppressive TME. Tamoxifen (Tmx) and Fe3+ are encapsulated into TAPP to achieve the combination of chemotherapy and chemodynamic therapy (CDT). Tmx directly downregulates HIF-1α, and a pillar[5]arene-based macrocyclic host successfully eliminates polyamines in tumors. Enhanced immunogenic cell death is achieved by Tmx and Fe3+, and the therapeutic efficacy is further synergized by immune checkpoint blockade (ICB) therapy. This supramolecular reprogramming modality encourages cytotoxic T lymphocyte infiltration, achieving pre-eminent immune response and long-term tumor suppression.


Assuntos
Calixarenos , Gastrópodes , Neoplasias , Animais , Microambiente Tumoral , Imunoterapia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
6.
Small ; 19(30): e2300217, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37021733

RESUMO

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.


Assuntos
Pontos Quânticos , Traumatismo por Reperfusão , Selênio , Humanos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Carbono , Lecitinas , Fígado , Traumatismo por Reperfusão/tratamento farmacológico
7.
World J Surg Oncol ; 21(1): 155, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37211596

RESUMO

OBJECTIVE: To investigate the predictive merit of combined preoperative nutritional condition and systemic inflammation on the prognosis of patients receiving esophagectomy, with the assessment of model construction to extract a multidisciplinary phantom having clinical relevance and suitability. METHODS: The software of R 4.1.2 was utilized to acquire the survival optimal truncation value and the confusion matrix of survival for the continuity variables. SPSS Statistics 26 was employed to analyze the correlation of parameters, where including t-test, ANOVA and the nonparametric rank sum test shall. Pearson chi-square test was used for categorical variables. The survival curve was retrieved by Kaplan-Meier method. Univariate analysis of overall survival (OS) was performed through log-rank test. Cox analysis was for survival analyze. The performance of the prediction phantom through the area under curve (AUC) of receiver operating characteristic curve (ROC), decision curve analysis (DCA), nomogram and clinical impact curve (CIC) was plotted by R. RESULTS: The AUC value of albumin-globulin score and skeletal muscle index (CAS) is markedly superior. Patients with diminished AGS and greater SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS) (P < 0.01). The CAS composite evaluation model was calibrated with better accuracy and predictive performance. The DCA and CIC indicated a relatively higher net revenue for the prediction model. CONCLUSIONS: The prediction model including the CAS score has excellent accuracy, a high net revenue, and favorable prediction function.


Assuntos
Esofagectomia , Nomogramas , Humanos , Esofagectomia/efeitos adversos , Prognóstico , Inflamação
8.
Proc Natl Acad Sci U S A ; 117(44): 27141-27147, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33024017

RESUMO

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.


Assuntos
Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Nanopartículas/uso terapêutico , Pneumonia Viral/terapia , Internalização do Vírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2 , Animais , Betacoronavirus , COVID-19 , Membrana Celular/química , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Células HEK293 , Humanos , Interleucina-6/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos ICR , Monócitos , Nanopartículas/química , Pandemias , Peptidil Dipeptidase A/metabolismo , Receptores de Citocinas/metabolismo , SARS-CoV-2 , Células THP-1
9.
Chem Soc Rev ; 51(4): 1336-1376, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35050284

RESUMO

Bioorthogonal chemistry is a powerful tool to site-specifically activate drugs in living systems. Bioorthogonal reactions between a pair of biologically reactive groups can rapidly and specifically take place in a mild physiological milieu without perturbing inherent biochemical processes. Attributed to their high selectivity and efficiency, bioorthogonal reactions can significantly decrease background signals in bioimaging. Compared with metal-catalyzed bioorthogonal click reactions, metal-free click reactions are more biocompatible without the metal catalyst-induced cytotoxicity. Although a great number of bioorthogonal chemistry-based strategies have been reported for cancer theranostics, a comprehensive review is scarce to highlight the advantages of these strategies. In this review, recent progress in cancer theranostics guided by metal-free bioorthogonal click chemistry will be depicted in detail. The elaborate design as well as the advantages of bioorthogonal chemistry in tumor theranostics are summarized and future prospects in this emerging field are emphasized.


Assuntos
Química Click , Neoplasias , Catálise , Humanos , Metais , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Medicina de Precisão
10.
Molecules ; 28(8)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37110674

RESUMO

With the development of personalized medical demands for precise diagnosis, rational management and effective cancer treatment, supramolecular theranostic systems have received widespread attention due to their reversibly switchable structures, sensitive response to biological stimuli and integration ability for multiple capabilities in a single platform with a programmable fashion. Cyclodextrins (CDs), benefiting from their excellent characteristics, such as non-toxicity, easy modification, unique host-guest properties, good biocompatibility, etc., as building blocks, serve as an all-purpose strategy for the fabrication of a supramolecular cancer theranostics nanodevice that is capable of biosafety, controllability, functionality and programmability. This review focuses on the supramolecular systems of CD-bioimaging probes, CD-drugs, CD-genes, CD-proteins, CD-photosensitizers and CD-photothermal agents as well as multicomponent cooperation systems with regards to building a nanodevice with functions of diagnosis and (or) therapeutics of cancer treatment. By introducing several state-of-the-art examples, emphasis will be placed on the design of various functional modules, the supramolecular interaction strategies under the fantastic topological structures and the hidden "bridge" between their structures and therapeutic efficacy, aiming for further comprehension of the important role of a cyclodextrin-based nanoplatform in advancing supramolecular cancer theranostics.


Assuntos
Ciclodextrinas , Neoplasias , Humanos , Ciclodextrinas/química , Medicina de Precisão , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
11.
J Nanobiotechnology ; 20(1): 24, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991595

RESUMO

Lymphatic system is identified the second vascular system after the blood circulation in mammalian species, however the research on lymphatic system has long been hampered by the lack of comprehensive imaging modality. Nanomaterials have shown the potential to enhance the quality of lymphatic imaging due to the unparalleled advantages such as the specific passive targeting and efficient co-delivery of cocktail to peripheral lymphatic system, ease molecular engineering for precise active targeting and prolonged retention in the lymphatic system of interest. Multimodal lymphatic imaging based on nanotechnology provides a complementary means to understand the kinetics of lymphoid tissues and quantify its function. In this review, we introduce the established approaches of lymphatic imaging used in clinic and summarize their strengths and weaknesses, and list the critical influence factors on lymphatic imaging. Meanwhile, the recent developments in the field of pre-clinical lymphatic imaging are discussed to shed new lights on the design of new imaging agents, the improvement of delivery methods and imaging-guided surgery strategies.


Assuntos
Sistema Linfático , Imagem Multimodal , Nanomedicina , Cirurgia Assistida por Computador , Animais , Humanos , Sistema Linfático/diagnóstico por imagem , Sistema Linfático/cirurgia , Camundongos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Ratos
12.
Med Sci Monit ; 28: e933503, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034089

RESUMO

BACKGROUND Junctional adhesion molecule-like protein (JAML) is a member of the junctional adhesion molecule family and mediates migration of immune cells, but its function in cancers remains unclear. This study aimed to evaluate the role of JAML in the prognosis and immune infiltrates of lung adenocarcinoma (LUAD). MATERIAL AND METHODS JAML expressions in LUAD tissues and normal tissues were compared using The Cancer Genome Atlas (TCGA) database and datasets from the Gene Expression Omnibus (GEO) database. The influence of JAML expression on prognosis was analyzed by Kaplan-Meier curve and Cox regression model. Interactive and functional analyses of JAML were performed by LinkedOmics and GeneMANIA databases. TIMER2.0, TISIDB, and GEPIA2 databases were used to investigate the correlation between JAML expression and immune infiltrates. RESULTS JAML expression was decreased in LUAD (P<0.001), and lower JAML expression was associated with worse outcomes of LUAD patients. High JAML expression was the protective factor for overall survival (OS) (HR 0.706, 95% CI 0.500-0.997, P=0.048). Interactive and functional analyses suggested that co-expressed genes with JAML have an obvious link to immune-related pathways. In addition, JAML expression was positively associated with infiltrating levels of CD8+ T cells, CD4+ T cells, B cells, dendritic cells, macrophages, and neutrophils, and had significant correlations with diverse immune marker sets in LUAD. CONCLUSIONS JAML expression was significantly correlated with prognosis and immune infiltrates. These preliminary findings suggested JAML could be considered as a potential prognostic biomarker and therapeutic target for LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Linfócitos do Interstício Tumoral/imunologia , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/imunologia , Idoso , Biomarcadores Tumorais/imunologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
13.
Proc Natl Acad Sci U S A ; 116(14): 6618-6623, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30894484

RESUMO

Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias Experimentais , Compostos Organoplatínicos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Química Click , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacocinética , Porfirinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Chem Soc Rev ; 50(4): 2839-2891, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33524093

RESUMO

Among the many challenges in medicine, the treatment and cure of cancer remains an outstanding goal given the complexity and diversity of the disease. Nanotheranostics, the integration of therapy and diagnosis in nanoformulations, is the next generation of personalized medicine to meet the challenges in precise cancer diagnosis, rational management and effective therapy, aiming to significantly increase the survival rate and improve the life quality of cancer patients. Different from most conventional platforms with unsatisfactory theranostic capabilities, supramolecular cancer nanotheranostics have unparalleled advantages in early-stage diagnosis and personal therapy, showing promising potential in clinical translations and applications. In this review, we summarize the progress of supramolecular cancer nanotheranostics and provide guidance for designing new targeted supramolecular theranostic agents. Based on extensive state-of-the-art research, our review will provide the existing and new researchers a foundation from which to advance supramolecular cancer nanotheranostics and promote translationally clinical applications.


Assuntos
Antineoplásicos/química , Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina de Precisão/métodos , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/farmacologia , Transporte Biológico , DNA/química , Humanos , Lipossomos/química , Nucleotídeos/química , Compostos Organometálicos/química , Proteínas/química
15.
Angew Chem Int Ed Engl ; 61(27): e202203786, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35384193

RESUMO

Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on ß-cyclodextrin/camptothecin (CPT) host-guest molecular recognition and iron-carboxylate coordination. Iron ions stabilizing SNPs catalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD-L1 checkpoint blockade, SNPs enables enhanced immune therapy and a long-term tumor remission.


Assuntos
Nanopartículas , Neoplasias , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Humanos , Ferro/uso terapêutico , Nanomedicina , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
16.
Angew Chem Int Ed Engl ; 61(52): e202213572, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36261392

RESUMO

Liposomes and polymersomes, typical vesicular drug delivery systems (DDSs), have faced some limitations in cancer theranostics. Suprasomes, supramolecular vesicles assembled from amphiphiles linked by noncovalent interactions, show potential as new generation of vesicular DDSs. We construct suprasomes based on host-guest recognition, by which the desired functions can be integrated into carriers without tedious synthesis. Photothermally active host-guest complex is formed between a functional guest and pillar[5]arene, which further self-assembles into hollow suprasomes. A supramolecular nanomedicine is developed by encapsulating cisplatin in the suprasomes. The obtained cisplatin@Suprasomes achieve excellent anticancer efficacy and anti-metastasis combining chemotherapy and photothermal therapy, which ablate the tumors without relapse and metastasis. This work demonstrates the facile functionalization of suprasomes, holding promise as alternatives to liposomes and polymersomes.


Assuntos
Lipossomos , Neoplasias , Humanos , Medicina de Precisão , Cisplatino , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
17.
Angew Chem Int Ed Engl ; 61(9): e202115208, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-34927320

RESUMO

Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over the past decade. However, it's still an open challenge to afford cylindrical nanostructures using polymeric building blocks via traditional self-assembly processes. Herein, we report a hierarchical self-assembly strategy of preparing cylindrical aggregates (tubisomes) from an amphiphilic supramolecular bottlebrush polymer in which a cyclic peptide nanotube is employed as the noncovalent backbone. Additionally, an aggregation-induced emission (AIE) effect was introduced into the tubisomes to endow them with excellent fluorescent properties. Intriguingly, by encapsulating with the anticancer drug doxorubicin (DOX), both the fluorescence of tubisome and DOX can be quenched due to the energy transfer relay (ETR) effect. The release of DOX can induce the interruption of the ETR effect and recover the silenced fluorescence, thereby permitting the in-situ imaging of drug release. The AIE-featured supramolecular tubisomes reported here provide an alternative approach for fabricating cylindrical polymeric nanostructures and holds great potential for imaging-guided drug delivery.


Assuntos
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Fluorescência , Humanos , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Nanoestruturas/química
18.
Eur J Clin Microbiol Infect Dis ; 40(5): 969-977, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33242168

RESUMO

To compare the diagnostic efficacy of CapitalBio Mycobacterium real-time polymerase chain reaction (RT-PCR) detection test and the first-generation Xpert MTB/RIF in smear-negative pulmonary tuberculosis (PTB). In this retrospective study of smear-negative PTB, we reviewed patient medical records to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test (positive result for either of the Xpert MTB/RIF and CapitalBio Mycobacterium detection tests) to evaluate their diagnostic accuracy against a composite reference standard. In total, 1553 patients were evaluated. The sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test were 57.1%, 92.9%, 81.1%, 95.9%, and 0.75; 53.4%, 97.7%, 98.6%, 41.5%, and 0.76; and 66.2%, 90.8%, 95.5%, 47.7%, and 0.79, respectively. For the bronchoalveolar lavage fluid (BALF) specimens, these values for Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test were 68.8%, 97.7%, 99.2%, 43.9%, and 0.83; 61.7%, 97.7%, 99.1%, 38.9%, and 0.80; and 77.0%, 95.5%, 98.6%, 50.9%, and 0.86, respectively. CapitalBio Mycobacterium detection test had moderate accuracy for smear-negative PTB, similar to Xpert MTB/RIF. The parallel test improved the sensitivity. BALF significantly improved the sensitivity and diagnostic accuracy of the test. The maximum diagnostic accuracy for smear-negative PTB was obtained with the parallel test and BALF specimens. BALF was the most effective specimen for diagnosing smear-negative PTB.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adulto , Idoso , Área Sob a Curva , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia
19.
J Nanobiotechnology ; 19(1): 330, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670552

RESUMO

BACKGROUND: Supramolecular theranostics have exhibited promising potentials in disease diagnosis and therapy by taking advantages of the dynamic and reversible nature of non-covalent interactions. It is extremely important to figure out the stability of the driving forces in physiological environment for the preparation of theranostic systems. METHODS: The host-guest complexation between cucurbit[8]uril (CB[8]), 4,4'-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV-vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine. RESULTS: Various experiments confirmed that the ternary complexation between 4,4'-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug. CONCLUSION: Arising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy.


Assuntos
Hidrocarbonetos Aromáticos com Pontes , Sistemas de Liberação de Medicamentos/métodos , Imidazóis , Nanomedicina Teranóstica/métodos , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/farmacocinética , Hidrocarbonetos Aromáticos com Pontes/toxicidade , Caproatos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Estabilidade de Medicamentos , Feminino , Células Hep G2 , Humanos , Imidazóis/química , Imidazóis/farmacocinética , Imidazóis/toxicidade , Lactonas/química , Camundongos , Camundongos Nus , Tomografia por Emissão de Pósitrons , Análise Espectral , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Angew Chem Int Ed Engl ; 60(15): 8018-8034, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32894628

RESUMO

Pyroptosis, a unique form of programmed cell death (PCD) that is characterized by DNA fragmentation, chromatin condensation, cellular swelling with big bubbles, and leakage of cell content, has been proven to have a close relationship with human diseases, such as inflammatory diseases and malignant tumors. Since a new gasdermin-D (GSDMD) protein was identified in 2015, various strategies have been developed to induce pyroptosis for cancer therapy, including ions, small-molecule drugs and nanomaterials. Although there are a number of reviews about the close relationship between the pyroptosis mechanism and the occurrence of various cancers, a summary covering recent progress in the field of nanomedicines in pyroptosis-based cancer therapy has not yet been presented. Therefore, it is urgent to fill this gap and light up future directions for the use of this powerful tool to combat cancer. In this Minireview, recent progress in cancer treatment based on pyroptosis induced by nanoparticles will be described in detail, the design highlights and the therapeutic advantages are emphasized, and future perspectives in this emerging area are proposed.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Nanotecnologia , Neoplasias/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Antineoplásicos/química , Humanos , Neoplasias/patologia , Piroptose/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química
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