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1.
World J Gastroenterol ; 25(36): 5469-5482, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576093

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional gas-troenterological diseases characterized by abnormal visceral sensitivity and low-grade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1ß, IL-6, and others) and express T cell immuno-globulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM: To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS: An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1ß and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrow-derived dendritic cells by in vitro experiments. RESULTS: The secretion of proinflammatory cytokines (IL-1ß and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1ß and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response. CONCLUSION: The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine.

2.
Nanoscale ; 11(32): 15195-15205, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380883

RESUMO

Mimicking the hierarchical microarchitecture of native myocardium in vitro plays an important role in cardiac tissue engineering. Here we present a novel strategy to produce multiscale conductive scaffolds with layer-specific fiber orientations for cardiac regeneration by combining solution-based and melt-based electrohydrodynamic (EHD) printing techniques. Polycaprolactone (PCL) microfibers were printed by melt-based EHD printing and the fiber orientation was flexibly controlled in a layer-by-layer manner according to user-specific design. The as-printed microfibrous scaffolds can provide the seeded cells necessary contact cues to guide layer-specific cellular alignments. Sub-microscale conductive fibers were simultaneously incorporated inside the well-organized PCL scaffolds by solution-based EHD printing, which significantly improved the conductivity as well as the cellular adhesion and proliferation capacity. The multiscale conductive scaffolds can further direct the multiple-layer alignments of primary cardiomyocytes and facilitate cardiomyocyte-specific gene expressions, which exhibited enhanced synchronous beating behavior compared with pure microfibrous scaffolds. It is envisioned that the proposed hybrid EHD printing technique might provide a promising strategy to fabricate multifunctional micro/nanofibrous scaffolds with biomimetic architectures, electrical conductivity and even biosensing properties for the regeneration of electroactive tissues.

3.
Am J Med Genet A ; 179(7): 1126-1138, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31058441

RESUMO

CHOPS syndrome is a multisystem disorder caused by missense mutations in AFF4. Previously, we reported three individuals whose primary phenotype included cognitive impairment and coarse facies, heart defects, obesity, pulmonary involvement, and short stature. This syndrome overlaps phenotypically with Cornelia de Lange syndrome, but presents distinct differences including facial features, pulmonary involvement, and obesity. Here, we provide clinical descriptions of an additional eight individuals with CHOPS syndrome, as well as neurocognitive analysis of three individuals. All 11 individuals presented with features reminiscent of Cornelia de Lange syndrome such as synophrys, upturned nasal tip, arched eyebrows, and long eyelashes. All 11 individuals had short stature and obesity. Congenital heart disease and pulmonary involvement were common, and those were seen in about 70% of individuals with CHOPS syndrome. Skeletal abnormalities are also common, and those include abnormal shape of vertebral bodies, hypoplastic long bones, and low bone mineral density. Our observation indicates that obesity, pulmonary involvement, skeletal findings are the most notable features distinguishing CHOPS syndrome from Cornelia de Lange syndrome. In fact, two out of eight of our newly identified patients were found to have AFF4 mutations by targeted AFF4 mutational analysis rather than exome sequencing. These phenotypic findings establish CHOPS syndrome as a distinct, clinically recognizable disorder. Additionally, we report three novel missense mutations causative for CHOPS syndrome that lie within the highly conserved, 14 amino acid sequence of the ALF homology domain of the AFF4 gene, emphasizing the critical functional role of this region in human development.

4.
ACS Appl Mater Interfaces ; 11(7): 6796-6808, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30673228

RESUMO

Self-healing, adhesive conductive hydrogels are of great significance in wearable electronic devices, flexible printable electronics, and tissue engineering scaffolds. However, designing self-healing hydrogels with multifunctional properties such as high conductivity, excellent mechanical property, and high sensitivity remains a challenge. In this work, the conductive self-healing nanocomposite hydrogels based on nanoclay (laponite), multiwalled carbon nanotubes (CNTs), and N-isopropyl acrylamide are presented. The presented nanocomposite hydrogels displayed good electrical conductivity, rapid self-healing and adhesive properties, flexible and stretchable mechanical properties, and high sensitivity to near-infrared light and temperature. These excellent properties of the hydrogels are demonstrated by the three-dimensional (3D) bulky pressure-dependent device, human activity monitoring device, and 3D printed gridding scaffolds. Good cytocompatibility of the conductive hydrogels was also evaluated with L929 fibroblast cells. These nanocomposite hydrogels have great potential for applications in stimuli-responsive electrical devices, wearable electronics, and so on.


Assuntos
Condutividade Elétrica , Hidrogéis/química , Movimento (Física) , Nanocompostos/química , Nanotubos de Carbono/química , Silicatos/química , Tecidos Suporte/química , Animais , Linhagem Celular , Humanos , Camundongos , Engenharia Tecidual
5.
Langmuir ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30500198

RESUMO

Monodisperse core-shell structured SiO2@poly(ionic liquid) (SiO2@PIL) particles are prepared by the polymerization of ionic liquid monomer on the surface of methacryloxypropyltrimethoxysilane modified SiO2 particles. The electroresponsive electrorheological (ER) effect of SiO2@PIL particles when dispersed in insulating carrier liquid is investigated and compared with pure poly(ionic liquid) (PIL) particles based on temperature-modulated rheology under electric fields. It demonstrates that hard SiO2 core not only enhances the ER effect of PIL particles but also improves the temperature dependence of ER effect. By dielectric spectroscopy analysis, the mechanism behind the property enhancement was discussed. It indicates that the hard SiO2 core can not only increase the interfacial polarization strength of SiO2@PIL particles by core-shell architecture but also restrain the segment relaxation or softening of PIL shell and influence the ion dynamics above the calorimetric glass transition of PILs by so called "substrate confinement effect", and this should be responsible for the enhanced electroresponsive ER effect and temperature stability of SiO2@PIL particles.

6.
Brain Res Bull ; 142: 216-223, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30075199

RESUMO

Lanthionine synthetase C-like protein 1 (LanCL1) is homologous to prokaryotic lanthionine cyclases, and has been shown to have novel functions in neuronal redox homeostasis. A recent study showed that LanCL1 expression was developmental and activity-dependent regulated, and LanCL1 transgene protected neurons against oxidative stress. In the present study, the potential protective effects of LanCL1 against ischemia was investigated in an in vitro model mimicked by oxygen and glucose deprivation (OGD) in neuronal HT22 cells. We found that OGD exposure induced a temporal increase and persistent decreases in the expression of LanCL1 at both mRNA and protein levels. Overexpression of LanCL1 by lentivirus (LV-LanCL1) transfection preserved cell viability, reduced lactate dehydrogenase (LDH) release and attenuated apoptosis after OGD. These protective effects were accompanied by decreased protein radical formation, lipid peroxidation and mitochondrial dysfunction. In addition, LanCL1 significantly stimulated mitochondrial enzyme activities and SOD2 deacetylation in a Sirt3-dependent manner. The results of western blot analysis showed that LanCL1-induced activation of Sirt3 was dependent on Akt-PGC-1α pathway. Knockdown of PGC-1α expression using small interfering RNA (siRNA) or blocking Akt activation using specific antagonist partially prevented the protective effects of LanCL1 in HT22 cells. Taken together, our results show that LanCL1 protects against OGD through activating the Akt-PGC-1α-Sirt3 pathway, and may have potential therapeutic value for ischemic stroke.

7.
ACS Appl Mater Interfaces ; 10(22): 19116-19122, 2018 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-29745637

RESUMO

Electrohydrodynamic (EHD) printing has been recently investigated as an effective technique to produce high-resolution conductive features. Most of the existing EHD printing studies for conductive features were based on metallic nanoparticle inks in a microdripping mode, which exhibited relatively low efficiency and commonly required high-temperature annealing process to achieve high conductivity. The EHD printing of high-resolution conductive features at a relatively low temperature and in a continuous cone-jetting mode is still challenging because the conductive inks might connect the charged nozzle, and the grounded conductive or semiconductive substrates to cause discharge and terminate the printing process. In this study, the EHD printing process of conductive polymers in a low-temperature cone-jetting mode was explored to fabricate conductive microstructures. The smallest width of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) lines was 27.25 ± 3.76 µm with a nozzle diameter of 100 µm. It was interesting to find that the electrohydrodynamically printed PEDOT:PSS-PEO features exhibited unique thermal properties when a dc voltage was applied. The conductive and thermal properties of the resultant features were highly dependent on the printing layer number. Microscale PEDOT:PSS features were further encapsulated into electrospun nanofibrous mesh to form a flexible sandwich structure. The EHD printing of PEDOT:PSS features with tunable conductive and thermal properties might be useful for the applications of flexible and wearable microdevices.

8.
Biomaterials ; 171: 178-197, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29698868

RESUMO

The clinical outcomes of conventional mono-chemotherapy of cancers are usually far from satisfactory due to some issues such as tumor heterogeneity and resistance to chemotherapeutic drugs. With the increasing knowledge of molecular signal pathways and pathological mechanisms involved in the initiation and progression of cancers, collaborative strategies have been elaborated to optimize therapeutic outcomes. This review surveys the most recent advances in combination therapy including combination chemotherapy, chemotherapy plus gene therapy, chemotherapy plus phototherapy, as well as chemotherapy plus immunotherapy. Additionally, chemotherapy-involved multiple therapy that merges various therapeutic modalities is also presented. We try to elicit the rationales of applying these combinational formulations for cancer chemotherapy, which might provide new guidelines for high-performance cancer treatments.

9.
Materials (Basel) ; 11(1)2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29361754

RESUMO

Additive manufacturing (AM) has drawn tremendous attention in various fields. In recent years, great efforts have been made to develop novel additive manufacturing processes such as micro-/nano-scale 3D printing, bioprinting, and 4D printing for the fabrication of complex 3D structures with high resolution, living components, and multimaterials. The development of advanced functional materials is important for the implementation of these novel additive manufacturing processes. Here, a state-of-the-art review on advanced material strategies for novel additive manufacturing processes is provided, mainly including conductive materials, biomaterials, and smart materials. The advantages, limitations, and future perspectives of these materials for additive manufacturing are discussed. It is believed that the innovations of material strategies in parallel with the evolution of additive manufacturing processes will provide numerous possibilities for the fabrication of complex smart constructs with multiple functions, which will significantly widen the application fields of next-generation additive manufacturing.

10.
ACS Appl Mater Interfaces ; 9(49): 42622-42632, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29148707

RESUMO

A facile and targeted gene delivery system was prepared by conjugating ß-cyclodextrin modified polyethylenimine (PEI-CD) and adamantyl peptide (AdGRGDS) based on host-guest interaction. With the rational design between PEI-CD and AdGRGDS, the PEI-CD/AdGRGDS gene delivery system showed excellent DNA binding capability and exhibited good ability to compact DNA into uniform spherical nanoparticles. In vitro luciferase assay showed that gene expression transfected by PEI-CD/AdGRGDS was stronger than that by PEI-CD in HeLa cells, whereas gene expression transfected by PEI-CD/AdGRGDS and PEI-CD was similar to each other in COS7 cells. Internalization of complexes was qualitatively studied using a confocal laser scanning microscope (CLSM) and quantitatively analyzed by flow cytometry, respectively, and targeting specificity was also evaluated by CLSM. Results of CLSM and flow cytometry indicated that PEI-CD/AdGRGDS had good targeting specificity to tumor cells with integrin αvß3 overexpression. To further evaluate the targeting specificity and transfection efficiency in vivo, a rat model with murine hepatic carcinoma cell line H22 was used. PEI-CD/AdGRGDS showed stronger gene expression efficiency than PEI-CD via in vivo transfection of pORF-LacZ and pGL-3 plasmids after subcutaneous injection. Interestingly, PEI-CD/AdGRGDS also showed high targeting specificity and transfection distribution to tumor xenograft after tail-vein injection. In vitro and in vivo assays highlighted the importance of GRGDS targeting specificity to tumor cells with integrin αvß3 overexpression and demonstrated that the PEI-CD/AdGRGDS gene delivery system would have great potential for targeted tumor therapy.

11.
Adv Mater ; 29(44)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29024101

RESUMO

Continuous exposure to carbon monoxide (CO) can sensitize cancer cells to chemotherapy while protect normal cells from apoptosis. The Janus face of CO thus provides an ideal strategy for cancer therapy. Here, a photocatalytic nanomaterial (HisAgCCN) is introduced to transform endogenous CO2 to CO for improving cancer therapy in vivo. The CO production rate of HisAgCCN reaches to 65 µmol h-1 gmat-1 , which can significantly increase the cytotoxicity of anticancer drug (doxorubicin, DOX) by 70%. Interestingly, this study finds that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells, whereas protect normal cells from chemotherapy-induced apoptosis as well. Proteomics and metabolomics studies reveal that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells specifically. In vivo studies indicate that HisAgCCN/DOX combination therapy presents a synergetic tumor inhibition, which might provide a new direction for clinical cancer therapy.

12.
ACS Nano ; 11(7): 7201-7214, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28686414

RESUMO

In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.

13.
Biomaterials ; 128: 136-146, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28325685

RESUMO

Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by ß-cyclodextrin (ß-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Retroalimentação Fisiológica , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Injeções Intravenosas , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Porosidade , Dióxido de Silício/química , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêutico
14.
Small ; 13(18)2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28266809

RESUMO

The nanoplatform GNR-ACPP-PpIX (designated as GNR-ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR-ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases-2 (MMP-2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special "U type" structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP-2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP-PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual-mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity.

15.
ACS Nano ; 11(2): 1419-1431, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28107631

RESUMO

In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing a hyaluronic acid (HA)-targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissues. The released DC depleted the Glut1 level in tumor cells and induced a cascade effect on cellular metabolism by inhibiting glucose uptake, blocking glycolysis, decreasing ATP levels, hampering heat shock protein (HSP) expression, and ultimately leaving malignant cells out from the protection of HSPs to stress (e.g., heat), and then tumor cells were more easy to kill. Owing to the sensitization effect of GNR/HA-DC, CD44 overexpressed tumor cells could be significantly damaged by PTT with an enhanced therapeutic efficiency in vitro and in vivo.

16.
Biosens Bioelectron ; 87: 73-80, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27522015

RESUMO

Herein, we report a novel quinoline derivative-based two-photon fluorescent probe 6-(dimethylamino)quinoline-2-benzothiazoline (HQ), which is capable of tracking superoxide anion in organisms with specific "turn-on" fluorescence response based on extension of π-conjugations and moderate ICT process. The probe exhibited favorable photophysical properties, a broad linear range and high photostability. It can specifically detect superoxide anion with a significant fluorescence enhancement and great linearity from 0 to 500µM in PBS buffer. Furthermore, HQ shows low cytotoxicity and excellent photostability toward living cells and organisms, which was able to monitor endogenous superoxide anion fluxes in living cells and in vivo. For the first time, endogenous superoxide anion in lung inflammation was visualized successfully by using HQ through two-photon microscopy, and the probe HQ shows great potential for fast in-situ detecting of inflammatory response in live organisms.


Assuntos
Benzotiazóis/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Imagem Óptica/métodos , Superóxidos/análise , Animais , Feminino , Inflamação/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Quinolinas/química , Células RAW 264.7 , Peixe-Zebra
17.
Nano Lett ; 17(1): 284-291, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28027643

RESUMO

Discovering advanced materials for regulating cell death is of great importance in the development of anticancer therapy. Herein, by harnessing the recently discovered oxidative stress regulation ability of p53 and the Fenton reaction inducing capability of metal-organic network (MON), MON encapsulated with p53 plasmid (MON-p53) was designed to eradicate cancer cells via ferroptosis/apoptosis hybrid pathway. After confirming the detailed mechanism of MON-p53 in evoking ferroptosis, we further discovered that MON-p53 mediated a "bystander effect" to further sensitize cancer cells toward the MON-p53 induced ferroptosis. A 75-day anticancer experiment indicated that MON-p53 treatment not only suppressed the tumor growth but also prolonged the life-span of tumor bearing mice. Owing to its ability to promote intracellular oxidative stress, MON-p53 decreased the blood metastasis, lung metastasis, and liver metastasis. As a consequence, discovering methods to induce cell ferroptosis would provide a new insight in designing anticancer materials.


Assuntos
Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Estruturas Metalorgânicas/administração & dosagem , Neoplasias/terapia , Polifenóis/química , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Morte Celular , Linhagem Celular Tumoral , Genes p53 , Terapia Genética , Humanos , Estruturas Metalorgânicas/farmacologia , Nanoestruturas , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Plasmídeos , Propriedades de Superfície
18.
ACS Appl Mater Interfaces ; 9(1): 255-265, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-27966867

RESUMO

Intracellularly biotriggered decomposition of gene vectors is generally thought to benefit transfection. However, the bioresponsiveness is far from satisfactory, and the exact role of biodecomposition in the transfection process remains unclear to date. To overcome the challenges, highly rapid bioresponse of vectors has to be achieved so as to greatly amplify the intracellular deviation compared with the noncontrolled pattern. To this end, a supramolecular polyrotaxane has been elaborately designed by integrating reversible dynamics of supramolecular assembly and chemically labile bonds, in order to effectively propel intracellular decomposition. Inside tumor cells, the redox-responsive bulk dissociation of the supramolecular vector readily took place and was further accelerated by the lysosomal-acidity-triggered terminal decomposition. Both the in vitro and in vivo experiments have demonstrated that this supramolecule could mediate considerably more rapid gene accumulation in nuclei than the nonresponsive controls including PEI25K, the gold standard of nonviral vectors. Along with the structural decomposition, the supramolecule simultaneously underwent the transition of fluorescence quenching, favoring the evaluation over the bioresponsiveness inside cells. Based on the resulting data, it is suggested that the biotriggered volume expansion of supramolecule/DNA complexes may be the major factor accounting for that dramatically accelerated transnuclear gene transport during cellular mitosis, thus affecting the transfection. This study offers an understanding of the intracellular gene transport from a new viewpoint.


Assuntos
Vetores Genéticos/genética , Núcleo Celular , DNA , Humanos , Oxirredução , Transfecção
19.
Biomaterials ; 117: 54-65, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27936417

RESUMO

Supramolecular photosensitizers (supraPSs) have emerged as effective photodynamic therapy (PDT) agents. Here, we propose the assembling capacity of supraPSs as a new strategy to construct theranostic nanoplatform with versatile functions aming at high-performance tumor therapy. By coating tirapazamine (TPZ)-loaded mesoporous silica nanoparticles (MSNs) with layer-by-layer (LbL) assembled multilayer, the versatile nanoplatform (TPZ@MCMSN-Gd3+) was obtained with the formation of supraPSs via host-guest interaction and the chelation with paramagnetic Gd3+. The TPZ@MCMSN-Gd3+ could be specifically uptaken by CD44 receptor overexpressed tumor cells and respond to hyaluronidase (HAase) to trigger the release of therapeutics. As confirmed by in vivo studies, TPZ@MCMSN-Gd3+ showed preferential accumulation in tumor site and significantly inhibited the tumor progression by the collaboration of PDT and bioreductive chemotherapy under NIR fluorescence/MR imaging guidance. Taken together, this supraPSs based strategy paves a new paradigm of the way for the construction of theranostic nanoplatform.


Assuntos
Antineoplásicos/administração & dosagem , Nanocápsulas/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Dióxido de Silício/química , Animais , Células COS , Cercopithecus aethiops , Cristalização/métodos , Feminino , Humanos , Células MCF-7 , Imagem por Ressonância Magnética/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência/métodos , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Nanoporos/ultraestrutura , Impressão Tridimensional , Nanomedicina Teranóstica/métodos , Tirapazamina , Resultado do Tratamento , Triazinas/administração & dosagem
20.
Biomaterials ; 117: 92-104, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27939904

RESUMO

In this work, mitochondria-targeting gold nanostar (AuNS) and anticarcinogen DOX were co-encapsulated in hyaluronic acid (HA) protective shell for tumor-targeting synergistic photothermal/chemo-therapy. Cationic peptide R8 and mitochondria-targeting pro-apoptotic peptide TPP-KLA were co-decorated on AuNS to form AuNS-pep via Au-S bonds. Then, electronegative HA was further coated on the surface via electrostatic interaction for cancer cell targeting. During the coating process, DOX was also introduced via electrostatic interaction to obtain a versatile nanoplatform AuNS-pep/DOX@HA. It was found that the nanoplatform could be internalized into tumor cells via CD44 receptor-mediated recognition. Followed digestion by hyaluronidase (HAase), the therapeutic nanoplatform was able to release DOX for chemotherapy and mitochondria-targeting nanoheater AuNS-pep for near infrared (NIR) light triggered subcellular photothermal therapy (PTT). This tumor-targeting nanoplatform AuNS-pep/DOX@HA displayed prominent non-resistant or resistant tumor inhibition both in vitro and in vivo.


Assuntos
Doxorrubicina/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Nanocápsulas/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Terapia Combinada/métodos , Doxorrubicina/química , Tratamento Farmacológico/métodos , Feminino , Ouro/administração & dosagem , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanocápsulas/química , Neoplasias Experimentais/patologia , Tamanho da Partícula , Resultado do Tratamento
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