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1.
Cell Prolif ; : e13613, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351579

RESUMO

Diabetic wounds impose significant burdens on patients' quality of life and healthcare resources due to impaired healing potential. Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)-based multiblock hydrogel, named poly (glycerol sebacate)-co-poly (ethylene glycol)-co-poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS-based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS-based hydrogels as advanced wound dressings for diabetic wound healing.

2.
Anal Chem ; 95(50): 18564-18571, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38060825

RESUMO

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Limite de Detecção , Simulação de Acoplamento Molecular , Medições Luminescentes/métodos , DNA , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
4.
Anal Chem ; 95(39): 14797-14804, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37737115

RESUMO

Given the lack of timely evaluation of the well-received selenium fortification, a neat lateral-flow chromatographic solution was constructed here by using the recently identified urinary selenosugar (Sel) as a strongly indicative marker. As there are no ready-made receptors for this synthetic standard, phenylboronic acid (PBA) esterification and Dolichos biflorus agglutinin (DBA) affinity joined up to pinch and pin down the analyte into a sandwich-type glycol complex. Pilot lectin screening on homemade glycan microarrays verified such a new pairing between dual recognizers as PBA-Sel-DBA with a firm monosaccharide-binding constant. To quell the sample autofluorescence, europium nanoparticles with efficient long-life afterglow were employed as conjugating probes under 1 µs excitation. After systematic process optimizations, the prepared Sel-dipstick achieved swift and sensitive fluorometry over the physiological level of the target from 0.1 to 10 µM with a detection limit down to 0.06 µM. Further efforts were made to eliminate matrix effects from both temperature and pH via an approximate formula. Upon completion, the test strips managed to quantify the presence of Sel in not just imitated but real human urine, with comparable results to those in the references. As far as we know, this would be the first in-house prototype for user-friendly and facile diagnosis of Se nutrition with fair accuracy as well as selectivity. Future endeavors will be invested to model a more traceable Se-supplementary plan based on the rhythmic feedback of Sel excretion.


Assuntos
Nanopartículas Metálicas , Selênio , Humanos , Európio , Sistemas Automatizados de Assistência Junto ao Leito , Cromatografia
5.
Discov Nano ; 18(1): 101, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37581715

RESUMO

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

6.
Biosensors (Basel) ; 13(4)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37185524

RESUMO

Polynucleotide kinase (PNK) is a key enzyme that is necessary for ligation-based DNA repair. The activity assay and inhibitor screening for PNK may contribute to the prediction and improvement of tumor treatment sensitivity, respectively. Herein, we developed a simple, low-background, and label-free method for both T4 PNK activity detection and inhibitor screening by combining a designed ligation-triggered T7 transcriptional amplification system and a crafty light-up malachite green aptamer. Moreover, this method successfully detected PNK activity in the complex biological matrix with satisfactory outcomes, indicating its great potential in clinical practice.


Assuntos
Técnicas Biossensoriais , Polinucleotídeo 5'-Hidroxiquinase , Bacteriófago T4 , Corantes de Rosanilina , Oligonucleotídeos , Técnicas Biossensoriais/métodos
7.
Hepatology ; 78(5): 1433-1447, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36800849

RESUMO

BACKGROUND AND AIMS: Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis. METHODS AND RESULTS: The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-ß-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-ß/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-ß, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)-mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)-mediated TrkB overexpression in hepatocytes. CONCLUSION: TGF-ß stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-ß/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo . These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.


Assuntos
Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Fator de Crescimento Transformador beta , Animais , Camundongos , Tetracloreto de Carbono , Células Estreladas do Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Proteína Tirosina Quinases , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Smad/genética , Proteínas Smad/metabolismo
8.
Anim Nutr ; 11: 171-180, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36254219

RESUMO

With the increasing demand for high-quality pork, more nutritional substances have been studied for the regulation of meat quality. Zero-dimensional fullerenes (C60) can modulate the biological behavior of a variety of cell lines and animals. In this study, we report the biological effects of C60 on finishing pigs at different concentrations. A total of 24 barrows (Duroc × Large White × Landrace), with an average body weight of 21.01 ± 0.98 kg, were divided into 3 groups and each treated daily with C60 (100 or 200 mg per kg feed) or a control diet until the end of the experiment. Our results showed that dietary C60 supplementation improved flesh color, marbling scores, and flavor amino acid contents of longissimus dorsi (LD) of growing-finishing pigs (P < 0.05). C60 improved meat quality by regulating lipid metabolism and muscle fiber morphology by mediating the expression of genes, L-lactic dehydrogenase (LDH), myosin heavy chain (MyHC) IIa, MyHCIIb, peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid transport protein 1 (FATP1) (P < 0.05). Moreover, C60 substantially promoted the mRNA expression of antioxidant enzyme genes (P < 0.05), which also contributed to improving meat quality. These findings have important implications for the application of C60 in the livestock industry, especially for improving the meat quality of fattening pigs.

9.
Dalton Trans ; 51(44): 16836-16844, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36314468

RESUMO

C70 is the second most abundant fullerene next to C60. In this work, the exploration of C70 based electrides is proposed by theoretical encapsulation of group I/II trimetallic clusters into the C70 cage. Herein, we provide computational evidence that endohedral metallofullerenes M3@C70 (M = Li, Na, K, Be, Mg, Ca, Sr, Ba) can exist stably by calculating encapsulation energies and analyzing atom centered density matrix propagation molecular dynamics simulations. According to the results of the atoms in molecules analysis, electron localization functions and nonlinear optical properties, M3@C70 (M = Li, Be, Mg, Ca) fullerenes are identified as electrides. Interestingly, Li3@C70 and Be3@C70 are the systems with better electride performances among alkali metal and alkaline earth metal systems, respectively. It is worth noting that C70 can improve the polarizability and first hyperpolarizability of electrides compared with C60. Our work unearths the potential of M3@C70 electride systems and paves the way for the research of C70-based electrides.

10.
ACS Appl Mater Interfaces ; 14(33): 37356-37368, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35951459

RESUMO

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanocompostos , Fotoquimioterapia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Irídio/farmacologia , Neoplasias Hepáticas/patologia , Nanocompostos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Sorafenibe/uso terapêutico
11.
J Nanobiotechnology ; 20(1): 188, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413984

RESUMO

BACKGROUND: Calcium ions (Ca2+) participates in various intracellular signal cascades and especially plays a key role in pathways relevant to cancer cells. Mitochondrial metabolism stimulated by calcium overload can trigger the opening of the mitochondrial permeability transition pore (MPTP), which leads to cancer cell death. METHODS: Herein, a mitochondrial pathway for tumour growth inhibition was built via the double-activation of MPTP channel. Fe2+ doped covalent organic frameworks (COF) was synthesised and applied as template to grow CaCO3 shell. Then O2 was storaged into Fe2+ doped COF, forming O2-FeCOF@CaCO3 nanocomposite. After modification with folic acid (FA), O2-FeCOF@CaCO3@FA (OFCCF) can target breast cancer cells and realize PDT/Ca2+ overload synergistic treatment. RESULTS: COF can induce the production of 1O2 under 650 nm irradiation for photodynamic therapy (PDT). Low pH and hypoxia in tumour microenvironment (TME) can activate the nanocomposite to release oxygen and Ca2+. The released O2 can alleviate hypoxia in TME, thus enhancing the efficiency of COF-mediated PDT. Abundant Ca2+ were released and accumulated in cancer cells, resulting in Ca2+ overload. Notably, the reactive oxygen species (ROS) and Ca2+ overload ensure the sustained opening of MPTP, which leads to the change of mitochondria transmembrane potential, the release of cytochrome c (Cyt c) and the activation of caspases 3 for cancer cell apoptosis. CONCLUSION: This multifunctional nanosystem with TME responded abilities provided a novel strategy for innovative clinical cancer therapy.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial , Neoplasias , Humanos , Cálcio/metabolismo , Hipóxia/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo
12.
Science ; 376(6590): 288-292, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35420967

RESUMO

Bulk chemicals such as ethylene glycol (EG) can be industrially synthesized from either ethylene or syngas, but the latter undergoes a bottleneck reaction and requires high hydrogen pressures. We show that fullerene (exemplified by C60) can act as an electron buffer for a copper-silica catalyst (Cu/SiO2). Hydrogenation of dimethyl oxalate over a C60-Cu/SiO2 catalyst at ambient pressure and temperatures of 180° to 190°C had an EG yield of up to 98 ± 1%. In a kilogram-scale reaction, no deactivation of the catalyst was seen after 1000 hours. This mild route for the final step toward EG can be combined with the already-industrialized ambient reaction from syngas to the intermediate of dimethyl oxalate.

13.
ACS Appl Mater Interfaces ; 13(39): 46334-46342, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34549583

RESUMO

Copper is vital for various life processes, whereas severely toxic at excess level. Intracellular copper homeostasis is strictly controlled by a set of transporters and chaperones encoded by the copper homeostasis genes. Increasing evidence has shown that copper is usually overloaded in multiple malignancies, including pancreatic cancer, which has an extremely poor prognosis. Recently, silencing the SLC31A1 gene, which encodes a major transmembrane copper transporter (CTR1), has been demonstrated to be an effective means for reducing the malignant degree of pancreatic cancer by downregulating the cellular copper levels. Herein, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to overcome the biological barriers for delivering small molecular RNAs and efficiently transferred two kinds of CTR1 mRNA-targeted RNA therapeutics, siCTR1 or miR-124, into PANC-1 cells. Both therapeutic tFNAs, termed t-siCTR1 and t-miR-124, prevented copper intake more effective than the free RNA therapeutics via efficiently suppressing the expression of CTR1, thereby significantly attenuating the progression of PANC-1 cells. In this study, therapeutic tFNAs are constructed to target metal ion transporters for the first time, which may provide an effective strategy for future treatment of other metal metabolism disorders.


Assuntos
Antineoplásicos/uso terapêutico , Cobre/metabolismo , DNA/química , Portadores de Fármacos/química , Neoplasias Pancreáticas/tratamento farmacológico , RNA Antissenso/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transportador de Cobre 1/metabolismo , Células HEK293 , Humanos , MicroRNAs/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Conformação de Ácido Nucleico , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
14.
Analyst ; 146(15): 4803-4810, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34241602

RESUMO

Pattern recognition, also called "array sensing," is a recognition strategy with a wide and expandable analysis range, based on high-throughput analysis data. In this work, we constructed a sensor array for the identification of targets including bacterial pathogens and proteins by using FAM-labeled DNA probes and 2D nanosheet materials. We designed an ordered and extendible DNA library for the collection of recognition probes. Unlike traditional DNA probes with random and massive sequences, our DNA library was constructed following a 5-digit binary number (00000-11111, 0 = CCC, and 1 = TTT), and especially, 8 special symmetry sequences were chosen from the library. Two different nanosheet materials were used as the quencher. When targets were added, the interaction between DNA and the nanosheets was competitively affected, and as a result, the fluorescence signal changed accordingly. Finally, by using our fluorescent sensor array, 17 bacteria and 8 proteins were precisely recognized. We believe that our work has provided a simple and valuable strategy for the improvement of the recognition range and discrimination precision for the development of pattern recognition.


Assuntos
Nanoestruturas , DNA/genética , Sondas de DNA/genética , Corantes Fluorescentes , Biblioteca Gênica , Espectrometria de Fluorescência
15.
Life (Basel) ; 11(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071941

RESUMO

Oxidative stress is involved in a wide variety of pathologies, and fullerene has been shown to have an antioxidant ability. Mycotoxins exert toxic effects through induction of excessive reactive oxygen species (ROS). Here, we evaluated water-soluble fullerene C60 for its anti-mycotoxin and antioxidant effects in vitro and in vivo. Intestinal epithelial cells were cultured with fullerene during deoxynivalenol (DON) exposure. The results revealed that fullerene C60 significantly promoted cell viability, decreased apoptosis and necrotic cell number, and significantly reduced intracellular ROS levels during DON exposure (p < 0.05). To investigate the role of fullerene in antioxidant capacity in vivo further, 40 three-week-old male C57BL/6 mice were randomly divided into four groups. There were no significant differences between the control and fullerene groups (p > 0.05). In mice exposed to DON, supplementation with fullerene C60 significantly improved growth performance, and enhanced the total antioxidant status and the activities of SOD and GPX in the intestine and liver (p < 0.05). In addition, fullerene C60 supplementation improved intestinal morphology, as indicated by a higher villus height and tight junction protein expression (p < 0.05). Furthermore, fullerene supplementation decreased serum concentrations of inflammatory cytokine and lipopolysaccharide (LPS; a penetrability marker) compared to the DON-challenged group (p < 0.05). The current study suggests that fullerene C60 improves intestinal antioxidant status against DON-induced oxidative stress in vitro and in vivo.

16.
ACS Appl Mater Interfaces ; 13(25): 29416-29423, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34148345

RESUMO

DNA self-assembled nanostructures have been considered as effective vehicles for biomolecule delivery because of their excellent biocompatibility, cellular permeability, noncytotoxicity, and small size. Here, we report an efficient antiviral strategy with self-assembled tetrahedral framework nucleic acids (tFNAs) delivering small interfering RNA (t-siRNA) to silence classical swine fever virus (CSFV) gene in porcine host cells. In this study, two previously reported siRNAs, C3 and C6, specifically targeting the CSFV genome were selected and modified on tFNAs, respectively, and termed t-C3 and t-C6. Results indicate that t-C3 and t-C6 can inhibit the viral proliferation of CSFV in kidney derived porcine cells, PK-15, effectively and that inhibition was markedly stronger than free siRNA-C3 or siRNA-C6 only. In addition, the DNA nanostructure also has high cargo-carrying capacity, allowing to deliver multiple functional groups. To improve the antiviral ability of tFNAs, a dual-targeting DNA nanostructure t-C3-C6 was constructed and used to silence the CSFV gene in porcine host cells. This study found that t-C3-C6 can inhibit the viral release and replication, exhibiting outstanding anti-CSFV capabilities. Therefore, these dual-targeting tFNAs have great potential in virus therapy. This strategy not only provides a novel method to inhibit CSFV replication in porcine cells but also verifies that tFNAs are effective tools for delivery of antiviral elements, which have great application potential.


Assuntos
Antivirais , Vírus da Febre Suína Clássica/efeitos dos fármacos , Portadores de Fármacos , Nanoestruturas/química , RNA Interferente Pequeno , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/farmacologia , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Suínos , Replicação Viral/efeitos dos fármacos
17.
Adv Healthc Mater ; 9(21): e2000650, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33000919

RESUMO

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), reveals a limited therapeutic effect due to a lack of selectivity and evident drug resistance. In the present study, bismuth-based mesoporous nanomaterial (NBOF) is loaded with SOR and then coated with polyethylene glycol and folic acid conjugates (P-FA) to form an NBOF@SOR-P-FA nanocarrier system. The system achieves significantly enhanced anti-cancer efficacy by combining chemotherapy with radiotherapy. To evaluate the effect of synergistic treatment, cytotoxicity detection, Live/Dead staining, apoptotic assay, and Western blot analysis are performed. The results suggest that NBOF@SOR-P-FA significantly inhibits HCC cell proliferation and promotes cell apoptosis. Also, the NBOF@SOR-P-FA exhibits excellent biocompatibility by hemolysis and serum biochemical tests and produces a substantially enhanced contrast efficiency as compared to iohexol by computed tomography imaging. More importantly, the profound suppression of tumor growth and potentiation of apoptosis are observed in a mouse subcutaneous tumor model. Collectively, these results indicate that the bismuth-based nanotheranostic platform could enhance the therapeutic effect of sorafenib and serve as an innovative method for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Bismuto/farmacologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Quimiorradioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Niacinamida , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico
18.
ACS Appl Mater Interfaces ; 12(43): 48357-48362, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33052659

RESUMO

Since H5N1 virus is a highly infectious pathogen that causes outbreaks of avian influenza, developing a sensitive and rapid diagnostic platform to sense it becomes significant. Here, a novel label-free fluorescence sensing platform based on DNA-templated silver nanoclusters (DNA-Ag NCs) is developed to detect the H5N1 gene sequence representing H5N1 virus. The three-segment-branched DNA structure with closed cytosine-rich loop is designed as an effective template to produce fluorescent Ag NCs, which is different with the previous design of cytosine-rich loop formed by hairpin-like single-stranded DNA or double-stranded DNA. The proposed fluorescence detection approach gives a wide linear range (500 pM-2 µM) and a low detection limit (500 pM) to sense H5N1 gene sequence. Furthermore, selective analysis of target DNA shows that our constructed analytical strategy has a high selectivity to H5N1 gene sequence. It is regarded as a promising method for highly sensitive and selective sensing of H5N1 virus.


Assuntos
Técnicas Biossensoriais , DNA/química , Fluorescência , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Nanopartículas Metálicas/química , Prata/química , Animais , Bovinos , Tamanho da Partícula , Soroalbumina Bovina/química , Propriedades de Superfície
19.
Oncol Rep ; 44(4): 1299-1313, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700744

RESUMO

Epithelial­mesenchymal transition (EMT), during which cancer cells lose the epithelial phenotype and gain the mesenchymal phenotype, has been verified to result in tumor migration and invasion. Numerous studies have shown that dysregulation of the Wnt/ß­catenin signaling pathway gives rise to EMT, which is characterized by nuclear translocation of ß­catenin and E­cadherin suppression. Wnt/ß­catenin signaling was confirmed to be affected by microRNAs (miRNAs), several of which are down­ or upregulated in metastatic cancer cells, indicating their complex roles in Wnt/ß­catenin signaling. In this review, we demonstrated the targets of various miRNAs in altering Wnt/ß­catenin signaling to promote or inhibit EMT, which may elucidate the underlying mechanism of EMT regulation by miRNAs and provide evidence for potential therapeutic targets in the treatment of invasive tumors.


Assuntos
MicroRNAs/metabolismo , Neoplasias/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Transição Epitelial-Mesenquimal , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , Proteínas Wnt/genética , beta Catenina/genética
20.
ACS Appl Mater Interfaces ; 12(15): 17193-17206, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32207914

RESUMO

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Indóis/química , Neoplasias Hepáticas/terapia , Nanocápsulas/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/uso terapêutico , Sorafenibe/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Indóis/metabolismo , Indóis/uso terapêutico , Isoindóis , Luz , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos , Camundongos Nus , Compostos Organometálicos/metabolismo , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Espécies Reativas de Oxigênio , Soroalbumina Bovina/química , Sorafenibe/metabolismo , Sorafenibe/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos de Zinco
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