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1.
J Colloid Interface Sci ; 581(Pt A): 31-43, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768733

RESUMO

The use of nanoscale metal-organic frameworks (MOFs) as drug delivery vehicles has attracted considerable attention in tumor therapy. In this study, novel biocompatible MOF-based nanocarriers were used as part of a facile and reproducible strategy for precision cancer theranostics. Both diagnostic (Mn2+) and therapeutic compounds (doxorubicin, DOX) were incorporated into the multifunctional MOF-based nanocarriers, which exhibited high colloidal stability and promoted T1-weighted proton relaxivity and low-pH-activated drug release. The obtained MOF-based nanocarriers exhibited significantly high cellular uptake and efficient intracellular drug delivery into cancer cells, which resulted in high apoptosis and cytotoxicity, in addition to effectively inhibiting the migration of 4T1 breast cancer cells. Moreover, the MOF-based nanocarriers could intensively deliver diagnostic and therapeutic agents to tumors to enable precise visualization of the nanocarrier accumulation and accurate tumor positioning, diagnosis, and imaging-guided therapy using magnetic resonance imaging (MRI). In addition, the functional MOF-based nanocarriers exhibited effective ablation of the primary breast cancer, as well as significant inhibition of lung metastasis with a high survival rate. Therefore, the developed nanocarriers represent a viable platform for cancer theranostics.

2.
Theranostics ; 10(10): 4557-4588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292515

RESUMO

In recent years, much progress has been motivated in stimuli-responsive nanocarriers, which could response to the intrinsic physicochemical and pathological factors in diseased regions to increase the specificity of drug delivery. Currently, numerous nanocarriers have been engineered with physicochemical changes in responding to external stimuli, such as ultrasound, thermal, light and magnetic field, as well as internal stimuli, including pH, redox potential, hypoxia and enzyme, etc. Nanocarriers could respond to stimuli in tumor microenvironments or inside cancer cells for on-demanded drug delivery and accumulation, controlled drug release, activation of bioactive compounds, probes and targeting ligands, as well as size, charge and conformation conversion, etc., leading to sensing and signaling, overcoming multidrug resistance, accurate diagnosis and precision therapy. This review has summarized the general strategies of developing stimuli-responsive nanocarriers and recent advances, presented their applications in drug delivery, tumor imaging, therapy and theranostics, illustrated the progress of clinical translation and made prospects.

3.
J Control Release ; 320: 314-327, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31954731

RESUMO

The systemic dosage regimen exhibited low therapeutic efficacy and incurred severe adverse effect, thus, the development of tumor-targeted therapeutics is crucial important for tumor precision therapy. Herein, the active targeted modulation of tumor microenvironments was schemed by developing hyaluronic acid-installed genomic nanocarriers (HA-NPs) for effectively ablation of both primary and metastatic tumors through anti-vascular endothelial growth factor (anti-VEGF) approach. The anti-VEGF genomic payloads were strategically packaged into the well-defined synthetic nanocarriers by layer-by-layer preparation strategy, exhibiting high colloidal stability and much lower cell viability than the cationic gene carriers. Besides, the HA-NPs could specifically and efficiently internalize with cancer cells for efficient intracellular gene delivery, leading to high gene transfection efficacy. Moreover, it further demonstrated efficient extravasation, high accumulation and deep penetration in tumors, which markedly facilitated tumor-targeted expression of anti-VEGF genomic payloads for inhabitation of neo-vasculature, consecutively contributing to potent ablation of solid tumors. In addition, the ligand-installed nanocarriers facilitated systemic treatment of melanoma lung metastasis by the expressed anti-VEGF proteins, which were extensively spread along blood circulation and metastatic niches to diminish the formation of neovasculature for tumorigenesis. Therefore, the proposed anti-VEGF genomic nanocarriers could shed intriguing implication in effectively treatment of primary tumors and metastasis.

4.
Adv Mater ; 32(13): e1902604, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31353770

RESUMO

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand-installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand-installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.

5.
Biomaterials ; 230: 119614, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31753475

RESUMO

The severe mortality and morbidity of myocardial infarction requests appropriate and accurate detection. Considering pathological profile of the acidic myocardial infarction microenvironments, herein, the low pH-sensitive albumin nanocomposites with MnO2 motifs (MnO2@BSA) have been engineered for T1-weighted MR imaging of myocardial infarction, while using non-pH-responsive Gd2O3@BSA nanocomposites as control. The nanocomposites were 20-30 nm in diameter with spheroid morphology. Besides, the MnO2@BSA have exhibited pH-triggered releasing of Mn2+, demonstrating approximately 38-fold and 55-fold increased molecular relaxivity at acute myocardial infarction-mimicking pH 6.5 (13.08 mM-1s-1) and macrophage intracellular pH 5.0 (18.76 mM-1s-1) compared to the extremely low relaxivity (0.34 mM-1s-1) at normal physiological conditions (pH 7.4). However, the Gd2O3@BSA with molecular relaxivity approximately 10 mM-1s-1 were without pH-sensitive properties. Furthermore, the MnO2@BSA have demonstrated high accumulation in the acute myocardial infarction regions and fast metabolism from the body after systemic injection, accounting high contrast enhancement for accurate MR imaging of acute myocardial infarction in rabbit models, demonstrating better diagnostic performance over the controls.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31558844

RESUMO

BACKGROUND: Alopecia areata (AA) is mainly a T cell-medicated autoimmune disease with non-scarring hair loss and limited treatment options. Of these, the patchy-type alopecia areata (AAP) is the most common and relatively easy to treat due to smaller areas of the scalp affected. To understand the pathogenesis of AAP and explore the therapeutic target, we focus on the molecular signatures by comparing AAP and normal subjects. METHODS: The gene expression profile (GSE68801) was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between AAP patients and normal controls using the GEO2R. Then the Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein interaction (PPI) network analysis were performed for DEGs. RESULTS: A total of 185 DEGs were identified, including 45 up-regulated genes and 140 down-regulated genes. The up-regulated DEGs were related to the immune response and chemokine signaling pathway. Meanwhile, down-regulated DEGs were enriched in keratin filament and intermediate filament. Subsequently, the top 10 hub genes were picked out in the PPI network, among them, CD2 showed the highest connectivity degree and central roles. CONCLUSION: Our data suggest that the CD2 may be a new therapeutic target for AAP. Further study is needed to explore the value of CD2 in the treatment of alopecia areata.

8.
Biomater Sci ; 7(10): 3942-3960, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414096

RESUMO

Calcium phosphate (CaP) was engineered as a drug delivery nanocarrier nearly 50 years ago due to its biocompatibility and biodegradability. In recent years, several approaches have been developed for the preparation of size-controllable, stable and multifunctional CaP nanocarriers, and several targeting moieties have also been decorated on the surface of these nanocarriers for active targeting. The CaP nanocarriers have been utilized for loading probes, nucleic acids, anticancer drugs and photosensitizers for cancer imaging, therapy and theranostics. Herein, we reviewed the recent advances in the preparation strategies of CaP nanocarriers and the applications of these nanocarriers in tumor diagnosis, gene delivery, drug delivery and theranostics and finally provided perspectives.


Assuntos
Antineoplásicos/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias/terapia , Animais , Fosfatos de Cálcio/química , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Nanomedicina Teranóstica
9.
Medicine (Baltimore) ; 98(6): e14297, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732145

RESUMO

OBJECTIVE: DNA methylation markers have been assessed as potential biomarkers for early cervical cancer detection. Herein, we evaluated the diagnostic performance of zinc finger protein 582 (ZNF582) methylation for cervical cancer detection. METHODS: Eligible studies were systematically searched from the electronic databases. The quality of enrolled studies was evaluated using the second version of the check list for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 14.0 software. Cochran's Q test and I statistics were applied to assess heterogeneity among studies. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. RESULTS: Seven studies composed of 1749 patients were eventually included. The pooled sensitivity of ZNF582 methylation was estimated to be 0.71 [95% confidence interval (CI): 0.67-0.75] in differentiating patients with cervical intraepithelial neoplasia type III/worse (CIN3+), corresponding to a specificity of 0.81 (95% CI: 0.79-0.83) and area under the curve (AUC) of 0.85. Our stratified analysis suggested that sequential combined of HPV DNA and ZNF582 methylation test (AUC, sensitivity, and specificity of 0.876, 0.75, and 0.87, respectively) achieved higher diagnostic accuracy than single HPV DNA testing test (AUC, sensitivity and specificity of 0.669, 0.96, and 0.41, respectively). CONCLUSIONS: ZNF582 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening. A new strategy of co-testing HPV DNA and ZNF582 methylation test in cervical scrapings confers an improved diagnostic accuracy than single HPV DNA testing.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Metilação de DNA , Fatores de Transcrição Kruppel-Like/metabolismo , Biomarcadores/metabolismo , Neoplasia Intraepitelial Cervical/etnologia , China , Feminino , Humanos
10.
J Biomed Nanotechnol ; 15(2): 373-381, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30596559

RESUMO

Efficient intracellular delivery of bioactive compounds into cancer cells is critically important for treatment, as some compounds only validate for therapy after entering cancer cells. The boron neutron capture therapy (BNCT) applies thermal neutron irradiation to react with 10B-compounds that existed inside cancer cells to generate secondary killing irradiations to eradicate cancer cells. The effective distance of the emitted secondary killing irradiations is as long as a cellular diameter, which requires the cellular uptake of 10B-compounds for efficient tumor BNCT. However, current clinical approved 10B-compound of sodium borocaptate (BSH) exhibits low cellular uptake by cancer cells, which limits the therapeutic efficacy. Herein, the multifunctional polymeric micelles with endosome escape and redox-responsive functions have been developed by self-assembly from the BSH-conjugated block copolymers for enhanced delivery of BSH into cancer cells. The BSH-loaded polymeric micelles (BSH/micelle) showed a hydrodynamic diameter around 50 nm, and the size distribution was monodisperse. The BSH/micelle were stable in normal physiological environment, while the BSH could be released in responding to high level of redox-potential in cancer cells. Besides, intracellular delivery of BSH was highly promoted by BSH/micelle through the endosome escape function of micelles, which further increased the tumor therapeutic efficacy by BNCT.


Assuntos
Terapia por Captura de Nêutron de Boro , Micelas , Sistemas de Liberação de Medicamentos , Endossomos , Oxirredução , Compostos de Sulfidrila
11.
J Control Release ; 295: 268-277, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30639386

RESUMO

Cancer stem-like cells (CSCs) treatment is a plausible strategy for enhanced cancer therapy. Here we report a glucose-installed sub-50-nm nanocarrier for the targeted delivery of small interfering RNA (siRNA) to CSCs through selective recognition of the glucose ligand to the glucose transporter 1 (GLUT1) overexpressed on the CSC surface. The siRNA nanocarrier was constructed via a two-step assembling process. First, a glucose-installed poly(ethylene glycol)-block-poly(l-lysine) modified with lipoic acid (LA) at the ω-end (Glu-PEG-PLL-LA) was associated with a single siRNA to form a unimer polyion complex (uPIC). Second, a 20 nm gold nanoparticle (AuNP) was decorated with ~65 uPICs through AuS bonding. The glucose-installed targeted nanoparticles (Glu-NPs) exhibited higher cellular uptake of siRNA payloads in a spheroid breast cancer (MBA-MB-231) cell culture compared with glucose-unconjugated control nanoparticles (MeO-NPs). Notably, the Glu-NPs became more efficiently internalized into the CSC fraction, which was defined by aldehyde dehydrogenase (ALDH) activity assay, than the other fractions, probably due to the higher GLUT1 expression level on the CSCs. The Glu-NPs elicited significantly enhanced gene silencing in a CSC-rich orthotopic MDA-MB-231 tumor tissue following systemic administration to tumor-bearing mice. Ultimately, the repeated administrations of polo-like kinase 1 (PLK1) siRNA-loaded Glu-NPs significantly suppressed the growth of orthotopic MDA-MB-231 tumors. These results demonstrate that Glu-NP is a promising nanocarrier design for CSC-targeted cancer treatment.


Assuntos
Neoplasias da Mama/terapia , Transportador de Glucose Tipo 1/genética , Ouro/química , Nanopartículas Metálicas/química , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi , Animais , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica , Glucose/química , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico
12.
Cancer Commun (Lond) ; 38(1): 35, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29914561

RESUMO

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope, boron-10, is irradiated with neutrons to produce high energy alpha particles. This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system. Two low molecular weight boron-containing drugs currently are being used clinically, boronophenylalanine (BPA) and sodium borocaptate (BSH). Although they are far from being ideal, their therapeutic efficacy has been demonstrated in patients with high grade gliomas, recurrent tumors of the head and neck region, and a much smaller number with cutaneous and extra-cutaneous melanomas. Because of their limitations, great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use. These include boron-containing porphyrins, amino acids, polyamines, nucleosides, peptides, monoclonal antibodies, liposomes, nanoparticles of various types, boron cluster compounds and co-polymers. Currently, however, none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies. Therefore, at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination, with the hope that future research will identify new and better boron delivery agents for clinical use.


Assuntos
Terapia por Captura de Nêutron de Boro/métodos , Boro/uso terapêutico , Neoplasias/radioterapia , Nêutrons/uso terapêutico , Boro/química , Boro/farmacocinética , Compostos de Boro/química , Compostos de Boro/farmacocinética , Compostos de Boro/uso terapêutico , Humanos , Isótopos/química , Isótopos/farmacocinética , Isótopos/uso terapêutico , Lipossomos/química , Lipossomos/farmacocinética , Neoplasias/metabolismo , Distribuição Tecidual
13.
Biomaterials ; 176: 60-70, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29860138

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Nanocompostos/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia/métodos , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Humanos , Nanopartículas de Magnetita/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanocápsulas/química , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/química , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Microambiente Tumoral
14.
Theranostics ; 8(11): 3138-3152, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29896308

RESUMO

Rationale: Cationic nanocarriers present with well-known toxicities, including inflammatory toxicity, which limit their clinical application. How the cationic nanocarrier-induced inflammatory response is negatively regulated is unknown. Herein, we found that following a sublethal dose of cationic nanocarriers, the induced inflammatory response is characterized by early neutrophil infiltration and spontaneous resolution within 1 week. Methods: C57BL/6 mice were intravenously injected with a dosage of 1-100 mg/kg cationic DOTAP liposomes as well as other cationic materials. Cell necrosis was detected by flow cytometry. Release of mitochondrial DNA was quantified by qPCR via Taqman probes. Signal proteins were detected by Western blotting. PGE2 production in the supernatant was quantitated using an enzyme immunoassay (EIA). The infiltrated inflammatory cells were observed in WT mice, Ccr2-/- mice, Sting-/- mice and Tlr9-/- mice. Results: The early stage (24-48 h) inflammatory neutrophil infiltration was followed by an increasing percentage of monocytes; and, compared with WT mice, Ccr2-/- mice presented with more severe pulmonary inflammation. A previously uncharacterized population of regulatory monocytes expressing both inflammatory and immunosuppressive cytokines was identified in this model. The alteration in monocyte phenotype was directly induced by mtDNA release from cationic nanocarrier-induced necrotic cells via a STING- or TLR9-dependent pathway. Neutrophil activation was specifically inhibited by PGE2 from Ly6C+ inflammatory monocytes, and intravenous injections of dual-phenotype monocytes beneficially modified the immune response; this inhibitory effect was abolished after treatment with indomethacin. Moreover, we provide clear evidence that mitochondrial DNA activated Ly6C+ monocytes and increased PGE2 production through TLR9- or STING-mediated MAPK-NF-κB-COX2 pathways. Conclusion: Our findings suggest that Ly6C+ monocytes and mtDNA-induced Ly6C+ monocyte PGE2 production may be part of a feedback mechanism that contributes to the resolution of cationic nanocarrier-induced inflammatory toxicity and may have important implications for understanding nanoparticle biocompatibility and designing better, safer drug delivery systems.


Assuntos
DNA Mitocondrial/metabolismo , Dinoprostona/metabolismo , Inflamação/induzido quimicamente , Monócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , Antígenos Ly/metabolismo , Materiais Biocompatíveis , Cátions , Feminino , Citometria de Fluxo , Inflamação/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Necrose/induzido quimicamente , Infiltração de Neutrófilos , Fenótipo
15.
J Biomed Nanotechnol ; 14(7): 1189-1207, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29944095

RESUMO

The tumor microenvironment (TME) is featured with aberrant vasculatures, specific physiological parameters, viscoelastic extracellular matrix and stromal cells, which are important factors in tumor initiation, development and metastasis. The components in TME form physical/biological barriers for drug delivery and therapy, and also contribute to resistance to treatment and immunosuppression. The advances in nanobiotechnology have offered a myriad of nanoparticles for targeting and treating tumors through the passive or active targeting strategies. However, the barriers in TME always limit the drug delivery and therapeutic efficacy of nanoparticles. To cope with this, recent strategies have employed nanoparticles to target and remodel tumor microenvironment, while a variety of nanoparticles have been developed with different functions for this score. In this review, we have described the typical features of tumor microenvironment along with their roles in tumor progression, and then focused on recent progresses in development and application of nanoparticles to target and remodel TME for enhanced cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Antineoplásicos , Humanos , Nanomedicina Teranóstica , Microambiente Tumoral
16.
Zhongguo Zhong Yao Za Zhi ; 43(8): 1554-1562, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29751700

RESUMO

Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This article would summarize the use status and research progress of Zha-xun by various ethnic groups all over the world, and the results show that it has various synonyms but most of them imply its most characteristic feature-outflow from the rock; Zha-xun resources are distributed in various places of the world, and its bearing spots are closely related to the geological structure; there are sharp arguments on the origins of Zha-xun, mainly including the minerals origin, biological fossils origin, biological origin, etc. Zha-xun has multiple functions and is mainly used to treat stomach disease, liver disease and rheumatoid arthritis in China, and premature ejaculation, impotence, vaginitis embolism in foreign countries. "Iron" Zha-xun is used into medicines both at home and abroad. According to ancient materia medica texts, it was mainly classified into five types, including gold Zha-xun, silver Zha-xun, copper Zha-xun, iron Zha-xun and lead Zha-xun mainly based on the predominance of color rather than the minerals contained. It is commonly believed by the domestic and foreign scholars that humic acid is the main medicinal part of Zha-xun, and their studies have found that it has a variety of pharmacological activities such as anti-ulcer, anti-inflammatory, liver protection, analgesia, immune regulation, increasing sexual desire and fertility, antioxidation, antibacterial, antidiabetic, antiepileptic, antipsychotic, etc. This paper provides a scientific basis for the rational utilization of Zha-xun resources.


Assuntos
Materia Medica , Medicina Tradicional Tibetana , China , Humanos , Masculino , Medicina Tradicional , Pesquisa
17.
Small ; 14(17): e1704440, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29611291

RESUMO

An intelligent theranostic nanoplatform based on nanovalve operated metal-organic framework (MOF) core-shell hybrids, incorporating tumorous microenvironment-triggered drug release, magnetic resonance imaging (MRI) guidance, sustained release, and effective chemotherapy in one pot is reported. The core-shell hybrids are constructed by an in situ growth method, in which Fe3 O4 particles with superior abilities of MRI and magnetic separation form the core and UiO-66 MOF with high loading capacity compose the shell, and then are surface-installed with pillararene-based pseudorotaxanes as tightness-adjustable nanovalves. This strategy endows the system with the ability of targeted, multistimuli responsive drug release in response to pH changes, temperature variations, and competitive agents. Water-soluble carboxylatopillar[6]arene system achieved sustained drug release over 7 days due to stronger host-guest binding, suggesting that the nanovalve tightness further reinforces the desirable release of anticancer agent over a prolonged time at the lesion site.

18.
Mater Sci Eng C Mater Biol Appl ; 83: 218-232, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29208282

RESUMO

The development of tumor-targeting nanocarriers is critical important for effective treatment. The synthetic polyesters have demonstrated high potential for developing nanocarriers for cancer theranostics. Especially, the biocompatible and biodegradable polyester micelles have held great promise for cancer therapy and diagnosis, while some candidates have been translated into clinical applications or under clinical trial. In this review, we have provided the state-of-the-art of polyester micelles for drug delivery and cancer theranostics. In addition, we have summarized several major types of polyesters used in the biomedical fields, the current clinical achievements of polyester micelles and recent progresses of multi-functional polyester micelles for tumor molecular imaging and therapeutic applications.


Assuntos
Poliésteres/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Micelas , Neoplasias/tratamento farmacológico , Polímeros/química , Nanomedicina Teranóstica/métodos
19.
Adv Sci (Weinh) ; 4(4): 1600285, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28435772

RESUMO

E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of cadherin-based functions. In this study, by fusing HAV and the classical tumor-targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis-inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects. This peptide is further processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel (DOC). Bioimaging analysis shows that peptide nanoparticles can penetrate into xenograft tumor cells with a significantly long retention in tumors and high tumor targeting specificity. In vivo, DOC/peptide NPs are substantially more effective at inhibiting tumor growth and prolonging survival compared with DOC control. Together, the findings of this study suggest that DOC/peptide NPs may have promising applications in pulmonary carcinoma therapy.

20.
J Control Release ; 254: 1-9, 2017 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-28336377

RESUMO

Boron neutron capture therapy is a promising tumor treatment method, though its wide application has been limited due to the poor tumor selectivity and intracellular delivery of 10B-compounds. Here, block copolymer-boron cluster conjugate based on the clinically used sodium borocaptate (BSH) and poly(ethylene glycol)-b-poly(glutamic acid) copolymer have been developed for effectively penetrating tumor tissues and homogeneously delivering the boron clusters into cancer cells towards safe and efficient boron neutron capture therapy. The PEGylated block copolymer-boron cluster (BSH) conjugate has demonstrated significant higher cellular uptake and tumor accumulation when compared to the non-PEGylated formulations and BSH. Moreover, the enhanced delivery to tumors of the conjugates, as well as their superior intratumoral penetration, which facilitated reaching the intracellular space of most cells in tumors, allowed the effective ablation of tumors after neutron irradiation.


Assuntos
Boroidretos/química , Terapia por Captura de Nêutron de Boro/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/radioterapia , Polietilenoglicóis/química , Ácido Poliglutâmico/química , Compostos de Sulfidrila/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Química Farmacêutica , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Permeabilidade
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