RESUMO
BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. METHODS: In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. RESULTS: We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48-72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. CONCLUSIONS: In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.
Assuntos
Antígenos B7 , Imunoterapia Adotiva , Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Humanos , Animais , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Imunoterapia Adotiva/métodos , Antígenos B7/metabolismo , Antígenos B7/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos , Proliferação de Células , Linfócitos T/imunologiaRESUMO
In contrast to the high efficiency of room temperature phosphorescence in crystal states, the generally utilized nanoparticles of organic materials in bioimaging demonstrated sharply decreased performance by orders of magnitude under physiological conditions, badly limiting the realization of their unique advantages. This case, especially for organic red/near-infrared (NIR) phosphorescence materials, is not only the challenge present in reality but more importantly, for the theoretical problem of deeply understanding and avoiding the quenching effect by oxygen and water toward excited triplet states. Herein, thanks to the intelligent molecular design by the introduction of abundant hydrophobic chains and highly-branched structures, bright and persistent red/NIR phosphorescence under physiological conditions has been realized, which demonstrated the shielding effect towards oxygen, and strengthened the intermolecular interactions to suppress the non-radiative transitions. Accordingly, the record phosphorescence intensity of nanoparticles in bioimage, up to 8.21 ± 0.36 × 108 p s-1 cm-2 sr-1, was achieved, to realize the clear phosphorescence imaging of liver and tumors in living mice, even lymph nodes in rabbit models with high SBRs. This work afforded an efficient way to achieve the bright red/NIR phosphorescence nanoparticles, guiding their further applications in biology and medicine.
RESUMO
Colloidal gold nanorods (GNRs) have demonstrated their potential to absorb light within specific wavelength bands and induce photothermal effects. However, the unpredictability and lack of adjustability in the broadband spectrum formed by the self-assembly of gold nanospheres or the coupling of various sizes of GNRs have posed significant challenges. To address this, we have developed broadband GNRs (BGNRs) with a predictable and adjustable extinction band in the visible and near-infrared regions. The BGNRs were synthesized by simply mixing GNRs with different aspect ratios, allowing for control over the bandwidths and positions of the extinction bands. Subsequently, the BGNRs were coated with silica and underwent surface modification. The resulting BGNRs@SiO2were then mixed with either polydimethylsiloxane (PDMS) or polyvinylidene fluoride (PVDF) to create BGNRs@SiO2/PDMS (or PVDF) films. The BGNRs@SiO2/PDMS and BGNRs@SiO2/PVDF films both exhibit excellent photothermal performance properties. Additionally, the light absorption intensity of the BGNRs@SiO2/PVDF film linearly increases upon folding, leading to significantly enhanced photothermal performance after folding. This work demonstrates that plasmonic colloidal GNRs, without the need for coupling, can yield predictable and adjustable extinction bands. This finding holds great promise for future development and practical applications, particularly in the transfer of these properties to films.
RESUMO
The chronic wound represents a serious disease characterized by a failure to heal damaged skin and surrounding soft tissue. Mesenchymal stem cells (MSCs) derived from adipose tissue (ADSCs) are a promising therapeutic strategy, but their heterogeneity may result in varying or insufficient therapeutic capabilities. In this study, we discovered that all ADSCs populations expressed platelet-derived growth factor receptor ß (PDGFR-ß), while the expression level decreased dynamically with passages. Thus, using a CRISPRa-based system, we endogenously overexpressed PDGFR-ß in ADSCs. Moreover, a series of in vivo and in vitro experiments were conducted to determine the functional changes in PDGFR-ß activation ADSCs (AC-ADSCs) and to investigate the underlying mechanisms. With the activation of PDGFR-ß, AC-ADSCs exhibited enhanced migration, survival, and paracrine capacity relative to control ADSCs (CON-ADSCs). In addition, the secretion components of AC-ADSCs contained more pro-angiogenic factors and extracellular matrix-associated molecules, which promoted the function of endothelial cells (ECs) in vitro. Additionally, in in vivo transplantation experiments, the AC-ADSCs transplantation group demonstrated improved wound healing rates, stronger collagen deposition, and angiogenesis. Consequently, our findings revealed that PDGFR-ß overexpression enhanced the migration, survival, and paracrine capacity of ADSCs and improved therapeutic effects after transplantation to diabetic mice.
Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Camundongos , Animais , Células Endoteliais , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Cicatrização , Células-Tronco Mesenquimais/metabolismo , Matriz Extracelular , Tecido AdiposoRESUMO
Background: Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitor is the cornerstone of acute coronary syndrome (ACS) management. Balancing the effects of different strategies of antiplatelet therapy including DAPT de-escalation, potent P2Y12 inhibitor monotherapy, and conventional DAPT is a hot topic. Methods: A systematic search was conducted from the MEDLINE, PubMed, and Embase through October 2021 to identify various DAPT strategies in randomized controlled trials (RCTs) for treatment of ACS patients after undergoing PCI with drug-eluting stent (DES). The network meta-analysis was performed to investigate the net clinic benefit of the DAPT de-escalation, potent P2Y12 inhibitor monotherapy, as well as conventional DAPT. The primary outcome was net adverse clinical events, defined as a composite of major bleeding and cardiac death, myocardial infarction, stroke, stent thrombosis, or target-vessel revascularization. The secondary outcomes include major adverse cardiac events and trial-defined major or minor bleeding. Results: A total of 14 RCTs with 63,982 patients were included. The DAPT de-escalation was associated with a lower risk of the primary outcome compared with potent P2Y12 inhibitor monotherapy (De-escalation vs monotherapy odds ratio (OR): 0.72 95% confidence interval (CI): 0.55-0.96), and other antiplatelet strategies (De-escalation vs clopidogrel + aspirin OR: 0.49 95% CI: 0.39-0.63; De-escalation vs prasugrel + aspirin OR: 0.76 95% CI: 0.59-0.98; De-escalation vs ticagrelor + aspirin OR: 0.76 95% CI: 0.55-0.90). There were no statistical differences in the incidence of bleeding (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.73 95% CI: 0.47-1.12) and major adverse cardiac events (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.79 95% CI: 0.59-1.08) between DAPT de-escalation and potent P2Y12 inhibitor monotherapy. Conclusions: This network meta-analysis showed that DAPT de-escalation would reduce the net adverse clinical events, compared with potent P2Y12 inhibitor monotherapy, for ACS patients undergone PCI treatment.
RESUMO
Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great deal of evidence has shown that histone methylation is closely related to hyperglycemia, insulin resistance, lipid and advanced glycation end products deposition, inflammatory and oxidative stress, endoplasmic reticulum stress and cell apoptosis, and these pathological factors play an important role in the pathogenesis of diabetic cardiomyopathy. In order to provide a novel theoretical basis and potential targets for the treatment of diabetic cardiomyopathy from the perspective of epigenetics, this review discussed and elucidated the association between histone methylation and the pathogenesis of diabetic cardiomyopathy in details.
Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Histonas , Humanos , Metilação , Estresse Oxidativo , Processamento de Proteína Pós-TraducionalRESUMO
OBJECTIVE: To investigate the value of single-sperm sequencing technology in preimplantation genetic testing. METHODS: Haplotypes were constructed by single-sperm isolation combined with single-sperm sequencing for a patient with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo mutation of the PKD1 gene c.3815T>G. 50. Single-sperm samples were isolated by mechanical braking, whole-genome amplification was performed, and mutation loci and their 187 upstream and downstream single nucleotide polymorphisms (SNP) were designed. The amplified products were verified for determination of the chromosome haplotypes carrying or not carrying pathogenic mutations. The embryos carrying pathogenic mutations were identified in 7 embryonic trophectoderm cell biopsy samples by high-throughput sequencing after whole-genome amplification. Available blastocysts were selected for embryo transfer, and amniotic fluid samples were collected at 18 weeks of gestation to determine whether the fetuses carried pathogenic mutations. RESULTS: A total of 30 SNPs were identified by single-sperm sequencing, and haplotypes were successfully constructed. Preimplantation haplotype analysis indicated that 5 embryos carried pathogenic mutations and 2 did not. mid-gestation amniotic fluid genetic testing revealed no PKD1 gene c.3815T>G mutation in the fetuses. CONCLUSION: SNPs can be identified by single-sperm sequencing in males carrying de novo pathogenic mutation, and haplotypes can be constructed by linkage analysis for preimplantation genetic testing of embryos.
Assuntos
Rim Policístico Autossômico Dominante , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Masculino , Rim Policístico Autossômico Dominante/genética , Sêmen , Testes Genéticos , Mutação , Sequenciamento de Nucleotídeos em Larga Escala , Espermatozoides , TecnologiaRESUMO
Stimuli-responsive multifunctional mesoporous silica nanoparticles (MSNs) have been studied intensively during the past decade. A large variety of mesopore capping systems have been designed, initially to show that it could be done and later for biomedical applications such as drug delivery and imaging. On-command release of cargo molecules such as drugs from the pores can be activated by a variety of stimuli. This paper focuses on three noninvasive, biologically usable external stimuli: magnetism, ultrasound, and light. We survey the variety of MSNs that have been and are being used and assess capping designs and the advantages and drawbacks of the nanoplatforms' responses to the various stimuli. We discuss important recent advances, their basic mechanisms, and their requirements for stimulation. On the basis of our survey, we identify fundamental challenges and suggest future directions for research that will unleash the full potential of these fascinating nanosystems for clinical applications.
Assuntos
Luz , Campos Magnéticos , Nanoestruturas/química , Dióxido de Silício/química , Nanomedicina Teranóstica , Ondas Ultrassônicas , Portadores de Fármacos/química , Humanos , Nanopartículas Magnéticas de Óxido de Ferro/química , PorosidadeRESUMO
Stationary source emissions of key industries, such as thermal power plants, have become the central consideration in environmental protection programs. Existing photoelectric sensors at stationary sources usually use a single wavelength laser to measure the total mass concentration of the particulate matter, bearing inherent errors due to the changing particle size distribution (PSD). However, the total mass concentration cannot comprehensively estimate the air pollution caused by the stationary sources. Therefore, it is required to measure both the mass concentration and PSD of the aerosols emitted by the stationary sources, based on which we can get a distributed mass concentration. To implement this, in this study, we designed a novel three-wavelength photoelectric sensor and tested its performance. Results showed that the prototype correctly determines the mean particle size and standard deviation of the PSDs and consequently adjusts the coefficient for measuring the mass concentration from light intensity, providing a comprehensive assessment of the pollutants.
RESUMO
In a closed system, it is well known that the time-reversal symmetry can lead to Kramers degeneracy and protect nontrivial topological states such as the quantum spin Hall insulator. In this Letter, we address the issue of whether these effects are stable against coupling to the environment, provided that both the environment and the coupling to the environment also respect time-reversal symmetry. By employing a non-Hermitian Hamiltonian with the Langevin noise term and utilizing the non-Hermitian linear response theory, we show that the spectral functions for Kramers degenerate states can be split by dissipation, and the backscattering between counterpropagating edge states can be induced by dissipation. The latter leads to the absence of accurate quantization of conductance in the case of the quantum spin Hall effect. As an example, we demonstrate this concretely with the Kane-Mele model. Our study can also include interacting topological phases protected by time-reversal symmetry.
RESUMO
Context: Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. Objective: The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Methods: Adult male Wistar rats were classified into six groups: normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Results: Daidzein as a flavonoid has antioxidant properties and shows in vitro antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H2O2), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. Conclusion: The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part via alteration of inflammatory cytokines.
Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/efeitos dos fármacos , Mucosa Esofágica/efeitos dos fármacos , Refluxo Gastroesofágico/tratamento farmacológico , Isoflavonas/farmacologia , Animais , Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Claudina-4/metabolismo , Claudina-5/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mucosa Esofágica/lesões , Esôfago/efeitos dos fármacos , Esôfago/metabolismo , Refluxo Gastroesofágico/induzido quimicamente , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Ratos , Ratos WistarRESUMO
AMPK is generally a tumor suppressor. However, once cancer arises, AMPK becomes a tumor promoter instead, driving cancer development. For such AMPK-driven cancers, AMPK blockade may be a valuable therapeutic strategy. Here we show that AMPK is upregulated in a variety of hematological cancers and plays key roles in maintaining viability of tumor cells. Blockade of AMPK signaling by dorsomorphin markedly induces apoptosis in Jurkat, K562 cell lines as well as primary cancerous B cells. Mechanistically, dorsomorphin significantly upregulates the expression of BAD, a pro-apoptotic member of the Bcl-2 gene family involved in initiating apoptosis. Reduction of BAD expression by RNA interference prevents apoptosis in response to AMPK inhibition. Thus, our data found BAD integrates the pro-apoptotic effects of dorsomorphin and provided novel insights into the mechanisms by which AMPK facilitates survival signaling in hematologic tumor cells.
Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Leucemia/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Proteína de Morte Celular Associada a bcl/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Células Jurkat , Células K562 , Leucemia/genética , Leucemia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
We report the experimental implementation of discrete-time topological quantum walks of a Bose-Einstein condensate in momentum space. Introducing stroboscopic driving sequences to the generation of a momentum lattice, we show that the dynamics of atoms along the lattice is effectively governed by a periodically driven Su-Schrieffer-Heeger model, which is equivalent to a discrete-time topological quantum walk. We directly measure the underlying topological invariants through time-averaged mean chiral displacements, which are consistent with our experimental observation of topological phase transitions. We then observe interaction-induced localization in the quantum-walk dynamics, where atoms tend to populate a single momentum-lattice site under interactions that are nonlocal in momentum space. Our experiment opens up the avenue of investigating discrete-time topological quantum walks using cold atoms, where the many-body environment and tunable interactions offer exciting new possibilities.
RESUMO
We report the experimental observation of tunable, nonreciprocal quantum transport of a Bose-Einstein condensate in a momentum lattice. By implementing a dissipative Aharonov-Bohm (AB) ring in momentum space and sending atoms through it, we demonstrate a directional atom flow by measuring the momentum distribution of the condensate at different times. While the dissipative AB ring is characterized by the synthetic magnetic flux through the ring and the laser-induced loss on it, both the propagation direction and transport rate of the atom flow sensitively depend on these highly tunable parameters. We demonstrate that the nonreciprocity originates from the interplay of the synthetic magnetic flux and the laser-induced loss, which simultaneously breaks the inversion and the time-reversal symmetries. Our results open up the avenue for investigating nonreciprocal dynamics in cold atoms, and highlight the dissipative AB ring as a flexible building element for applications in quantum simulation and quantum information.
RESUMO
Dental plaque is a high-incidence health concern, and it is caused by Streptococcus mutans. Dextranase can specifically hydrolyze É-1,6-glycosidic linkages in dextran. It is commonly used in the sugar industry, in the production of plasma substitutes, and the treatment and prevention of dental plaque. In this research work, we successfully cloned and expressed a cold-adapted dextranase from marine bacteria Catenovulum sp. DP03 in Escherichia coli. The recombinant dextranase named Cadex2870 contained a 2511 bp intact open reading frame and encoded 836 amino acids. The expression condition of recombinant strain was 0.1 mM isopropylthio-galactoside (IPTG), and the reduced temperature was 16 °C. The purified enzyme activity was 16.2 U/mg. The optimal temperature and pH of Cadex2870 were 45 °C and pH 8, and it also had catalytic activity at 0 °C. The hydrolysates of Cadex2870 hydrolysis Dextran T70 are maltose, maltotetraose, maltopentose, maltoheptaose and higher molecular weight maltooligosaccharides. Interestingly, 0.5% sodium benzoate, 2% xylitol, 0.5% sodium fluoride, 5% propanediol, 5% glycerin and 2% sorbitol can enhance stability Cadex2870, which are additives in mouthwashes. Additionally, Cadex2870 reduced the formation of dental plaque and effectively degraded formed plaque. Therefore, Cadex2870 shows great promise in commercial applications.
Assuntos
Alteromonadaceae , Organismos Aquáticos , Proteínas de Bactérias , Placa Dentária/tratamento farmacológico , Dextranase , Expressão Gênica , Streptococcus mutans/crescimento & desenvolvimento , Aclimatação , Alteromonadaceae/enzimologia , Alteromonadaceae/genética , Organismos Aquáticos/enzimologia , Organismos Aquáticos/genética , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/farmacologia , Temperatura Baixa , Placa Dentária/microbiologia , Dextranase/biossíntese , Dextranase/genética , Dextranase/isolamento & purificação , Dextranase/farmacologia , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologiaRESUMO
Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-ß signaling and subsequently affecting the pathophysiological roles of TGF-ß, including those in liver malignancy. KLF2, a member of the Krüppel-like factor (KLF) family transcription factors, has been implicated in impeding hepatocellular carcinoma (HCC) development. However, the underlying molecular mechanisms are not fully understood. In the present study, we found that TGF-ß stimulates the expression of KLF2 gene in several HCC cell lines. KLF2 protein is able to inhibit TGF-ß/Smad signaling in HCC cells as assessed by luciferase reporter assay. Further studies indicated that KLF2 inhibits the transcriptional activity of Smad2/3 and Smad4 and ameliorates TGF-ß-induced target gene expression, therefore creating a novel negative feedback loop in TGF-ß signaling. Functionally, stably expression of KLF2 in HCCLM3 cells attenuated TGF-ß-induced cancer cell motility in wound-healing and transwell assays by interfering with TGF-ß-mediated upregulation of MMP2. Together, our results revealed that KLF2 protein has a tumor-suppressive function in HCC through a negative feedback loop over TGF-ß signaling.
Assuntos
Carcinoma Hepatocelular/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/genética , Fator de Crescimento Transformador beta/genéticaRESUMO
Nanoparticle assemblies have generated intense interest because of their novel optical, electronic, and magnetic properties that open up numerous opportunities in fundamental and applied nanophotonics, -electronics, and -magnetics. However, despite the great scientific and technological potential of these structures, it remains an outstanding challenge to reliably fabricate such assemblies with both nanometer-level structural control and precise spatial arrangements on a macroscopic scale. It is the combination of these two features that is key to realizing nanoparticle assemblies' potential, particular for device applications. To address this challenge, we propose a hierarchical assembly approach consisting of both template-particle and particle-particle interactions, whereby the former ensures precise addressability of assemblies on a surface and the latter provides nanometer-level structural control. Template-particle interactions are harnessed via chemical-pattern-directed assembly, and the particle-particle interactions are controlled using DNA-directed self-assembly. To demonstrate the potential of this hierarchical assembly approach, we demonstrate the fabrication of a particularly fascinating assembly: the nanoparticle heterodimer, which possesses a surprisingly rich set of plasmonic properties and is a promising candidate to enable a variety of imaging and sensing applications. Each heterodimer is placed on the surface at predetermined locations, and the precise control of the nanogaps is confirmed by far-field scattering measurements of individual dimers. We further demonstrate that the gap size can be effectively tuned by varying the DNA length. By correlating measured spectra with finite-difference time-domain (FDTD) simulations, we determine the gap sizes to be 4.2 and 5.0 nm-with subnm deviation-for the two DNA lengths investigated. This is one of the best gap uniformities ever demonstrated for surface-bound nanoparticle assemblies. The estimated surface-enhanced Raman scattering (SERS) enhancement factor of these heterodimers is on the order of 105-106 with high reproducibility and predictable polarization-dependence. This hierarchical fabrication technique-employing both template-particle and particle-particle interactions-constitutes a novel platform for the realization of functional nanoparticle assemblies on surfaces and thereby creates new opportunities to implement these structures in a variety of applications.
RESUMO
Integrating multiple strategies of antibacterial mechanisms into one has been proven to have tremendous promise for improving antimicrobial efficiency. Hence, dual-valent platinum nanoparticles (dvPtNPs) with a zero-valent platinum core (Pt0 ) and bi-valent platinum shell (Pt2+ ions), combining photothermal and photodynamic therapy, together with "chemotherapy," emerge as spatiotemporally light-activatable platinum nano-antibiotics. Under near-infrared (NIR) exposure, the multiple antibacterial modes of dvPtNPs are triggered. The Pt0 core reveals significant hyperthermia via effective photothermal conversion while an immediate release of chemotherapeutic Pt2+ ions occurs through hyperthermia-initiated destabilization of metallic interactions, together with reactive oxygen species (ROS) level increase, thereby resulting in synergistic antibacterial effects. The precise cooperative effects between photothermal, photodynamic, and Pt2+ antibacterial effects are achieved on both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, where bacterial viability and colony-forming units are significantly reduced. Moreover, similar results are observed in mice subcutaneous abscess models. Significantly, after NIR treatment, dvPtNP exhibits a more robust bacteria-killing efficiency than other PtNP groups, owing to its integration of dramatic damage to the bacterial membrane and DNA, and alteration to ATP and ROS metabolism. This study broadens the avenues for designing and synthesizing antibacterial materials with higher efficiency.
Assuntos
Antibacterianos/farmacologia , Luz , Nanopartículas/química , Platina/farmacologia , Animais , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Feminino , Nanopartículas Metálicas/ultraestrutura , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Células NIH 3T3RESUMO
Dextranase, a hydrolase that specifically hydrolyzes α-1,6-glucosidic bonds, has been used in the pharmaceutical, food, and biotechnology industries. In this study, the strain of Catenovulum agarivorans MNH15 was screened from marine samples. When the temperature, initial pH, NaCl concentration, and inducer concentration were 30 °C, 8.0, 5 g/L, and 8 g/L, respectively, it yielded more dextranase. The molecular weight of the dextranase was approximately 110 kDa. The maximum enzyme activity was achieved at 40 °C and a pH of 8.0. The enzyme was stable at 30 °C and a pH of 5-9. The metal ion Sr2+ enhanced its activity, whereas NH4+, Co2+, Cu2+, and Li+ had the opposite effect. The dextranase effectively inhibited the formation of biofilm by Streptococcus mutans. Moreover, sodium fluoride, xylitol, and sodium benzoate, all used in dental care products, had no significant effect on dextranase activity. In addition, high-performance liquid chromatography (HPLC) showed that dextran was mainly hydrolyzed to glucose, maltose, and maltoheptaose. The results indicated that dextranase has high application potential in dental products such as toothpaste and mouthwash.