Project description:Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection.SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus.
Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the world. It is urgent to search for safe and effective therapies to address the CRC crisis. The siRNA-based RNA interference targeted silencing of PD-L1 has extensive potential in CRC treatment but is limited by the lack of efficient delivery vectors. In this work, the novel cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs)/siPD-L1 co-delivery vectors AuNRs@MS/CpG ODN@PEG-bPEI (ASCP) were successfully prepared by two-step surface modification of CpG ODNs-loading and polyethylene glycol-branched polyethyleneimine-coating around mesoporous silica-coated gold nanorods. ASCP promoted dendritic cells (DCs) maturation by delivering CpG ODNs, exhibiting excellent biosafety. Next, mild photothermal therapy (MPTT) mediated by ASCP killed tumor cells and released tumor-associated antigens, further promoting DC maturation. Furthermore, ASCP exhibited mild photothermal heating-enhanced performance as gene vectors, resulting in an increased PD-L1 gene silencing effect. Enhanced DCs maturity and enhanced PD-L1 gene silencing significantly promoted the anti-tumor immune response. Finally, the combination of MPTT and mild photothermal heating-enhanced gene/immunotherapy effectively killed MC38 cells, leading to strong inhibition of CRC. Overall, this work provided new insights into the design of mild photothermal/gene/immune synergies for tumor therapy and may contribute to translational nanomedicine for CRC treatment.
Project description:Photoacoustic signal generation by metal nanoparticles relies on the efficient conversion of light to heat, its transfer to the environment, and the production of pressure transients. In this study we demonstrate that a dielectric shell has a strong influence on the amplitude of the generated photoacoustic signal and that silica-coated gold nanorods of the same optical density are capable of producing about 3-fold higher photoacoustic signals than nanorods without silica coating. Spectrophotometry measurements and finite difference time domain (FDTD) analysis of gold nanorods before and after silica coating showed only an insignificant change of the extinction and absorption cross sections, hence indicating that the enhancement is not attributable to changes in absorption cross section resulting from the silica coating. Several factors including the silica thickness, the gold/silica interface, and the surrounding solvent were varied to investigate their effect on the photoacoustic signal produced from silica-coated gold nanorods. The results suggest that the enhancement is caused by the reduction of the gold interfacial thermal resistance with the solvent due to the silica coating. The strong contrast enhancement in photoacoustic imaging, demonstrated using phantoms with silica-coated nanorods, shows that these hybrid particles acting as "photoacoustic nanoamplifiers" are high efficiency contrast agents for photoacoustic imaging or photoacoustic image-guided therapy.
Project description:Photo-nanotheranostics integrates near-infrared (NIR) light-triggered diagnostics and therapeutics, which are combined into a novel all-in-one phototheranostic nanomaterial that holds great promise for the early detection and precise treatment of cancer. In this study, we developed methylene blue-loaded mesoporous silica-coated gold nanorods on graphene oxide (MB-GNR@mSiO2-GO) as an all-in-one photo-nanotheranostic agent for intracellular surface-enhanced Raman scattering (SERS) imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer. Amine functionalization of the MB-GNR@mSiO2 surfaces was performed using 3-aminopropyltriethoxysilane (APTES), which was well anchored on the carboxyl groups of graphene oxide (GO) nanosheets uniformly, and showed a remarkably higher photothermal conversion efficiency (48.93%), resulting in outstanding PTT/PDT for cancer. The in vitro photothermal/photodynamic effect of MB-GNR@mSiO2-GO with laser irradiation showed significantly reduced cell viability (6.32%), indicating that MB-GNR@mSiO2-GO with laser irradiation induced significantly more cell deaths. Under laser irradiation, MB-GNR@mSiO2-GO showed a strong SERS effect, which permits accurate cancer cell detection by SERS imaging. Subsequently, the same Raman laser can focus on highly detected MDA-MB-23l cells for a prolonged time to perform PTT/PDT. Therefore, MB-GNR@mSiO2-GO has great potential for precise SERS imaging-guided synergistic PTT/PDT for cancer.
Project description:The mechanism of mercury (Hg) amalgamation in gold nanorods coated with a mesoporous silica shell (AuNRs@mSiO2) and the effect of chemical treatments on the localized surface plasmon resonance (LSPR) spectral changes in single amalgamated AuNRs@mSiO2 remains unclear. In this study, we investigated Hg amalgamation and inward Hg diffusion in single AuNRs@mSiO2 without structural deformation via dark-field scattering spectroscopy and X-ray photoelectron spectroscopy. Then, we investigated the chemisorption of thiol molecules on single amalgamated AuNRs@Hg-mSiO2. Unlike previous studies on single AuNRs, the thiolation on single AuNRs@Hg-mSiO2 resulted in a redshift and line width narrowing of the LSPR peak within 1 h. To determine the chemical effect, we investigated the competition between two surface damping pathways: metal interface damping (MID) and chemical interface damping (CID). When we exposed amalgamated AuNRs@Hg-mSiO2 to 1-alkanethiols with three different carbon chain lengths for 1 h, we observed an increase in the line width broadening with longer chain lengths owing to enhanced CID, demonstrating the tunability of CID and LSPR properties upon chemical treatments. We also investigated the competition between the two surface damping pathways as a function of the time-dependent Au-Hg surface properties in AuNRs@Hg-mSiO2. The 24-h Hg treatment resulted in increased line width broadening compared to the 1-h treatment for the same thiols, which was attributed to the predominance of CID. This was in contrast to the predominance of MID under the 1-h treatment, which formed a core-shell structure. Therefore, this study provides new insights into the Hg amalgamation process, the effect of chemical treatments, competition between surface decay pathways, and LSPR control in AuNRs@mSiO2.
Project description:Engineering magnetic proximity effects-based devices requires developing efficient magnetic insulators. In particular, insulators, where magnetic phases show dramatic changes in texture on the nanometric level, could allow us to tune the proximity-induced exchange splitting at such distances. In this paper, we report the fabrication and characterization of highly ordered two-dimensional arrays of LaFeO3 (LFO)-CoFe2O4 (CFO) biphasic magnetic nanowires, grown on silicon substrates using a unique combination of bottom-up and top-down synthesis approaches. The regularity of the patterns was confirmed using atomic force microscopy and scanning electron microscopy techniques, whereas magnetic force microscopy images established the magnetic homogeneity of the patterned nanowires and absence of any magnetic debris between the wires. Transmission electron microscopy shows a close spatial correlation between the LFO and CFO phases, indicating strong grain-to-grain interfacial coupling, intrinsically different from the usual core-shell structures. Magnetic hysteresis loops reveal the ferrimagnetic nature of the composites up to room temperature and the presence of a strong magnetic coupling between the two phases, and electrical transport measurements demonstrate the strong insulating behavior of the LFO-CFO composite, which is found to be governed by Mott-variable range hopping conduction mechanisms. A shift in the Raman modes in the composite sample compared to those of pure CFO suggests the existence of strain-mediated elastic coupling between the two phases in the composite sample. Our work offers ordered composite nanowires with strong interfacial coupling between the two phases that can be directly integrated for developing multiphase spin insulatronic devices and emergent magnetic interfaces.
Project description:Macroscopically long wire-like arrangements of gold nanoparticles were obtained by controlled evaporation and partial coalescence of an aqueous colloidal solution of capped CTAB-Au nanorods onto a functionalised 3-mercaptopropyl trimethoxysilane (MPTMS) silicon substrate, using a removable, silicon wafer with a hydrophobic surface that serves as a "handrail" for the initial nanorods' linear self-assembly. The wire-like structures display a quasi-continuous pattern by thermal annealing of the gold nanorods when the solvent (i.e. water) is evaporated at temperatures rising from 20°C to 140°C. Formation of both single and self-replicating parallel 1D-superstructures consisting of two or even three wires is observed and explained under such conditions.
Project description:We present a cancer nanomedicine based on acidic pH targeted gold nanorods designed for multispectral optoacoustic tomography (MSOT). We have designed gold nanorods coated with mesoporous silica and subsequently capped with chitosan (CMGs). We have conjugated pH-sensitive variant 7 pHLIP peptide to the CMGs (V7-CMG) to provide targeting specificity to the acidic tumor microenvironment. In vitro, treatment of S2VP10 and MiaPaca2 cells with V7-CMG containing gemcitabine resulted in significantly greater cytotoxicity with 97% and 96.5% cell death, respectively than gemcitabine alone 60% and 76% death at pH 6.5 (S2VP10 pH 6.5 p=0.009; MiaPaca2 pH 6.5 p=0.0197). In vivo, the V7-CMGs provided the contrast and targeting specificity necessary for MSOT of retroperitoneal orthotopic pancreatic tumors. In the in vivo S2VP10 model, the V7-CMG particle preferentially accumulated within the tumor at 17.1 MSOT a.u. signal compared with 0.7 MSOT a.u. in untargeted CMG control in tumor (P = 0.0002). Similarly, V7-CMG signal was 9.34 MSOT a.u. in the S2013 model compared with untargeted CMG signal at 0.15 MSOT a.u. (P = 0.0004). The pH-sensitivity of the targeting pHLIP peptide and chitosan coating makes the particles suitable for simultaneous in vivo tumor imaging and drug delivery.
Project description:Mesoporous silica nanoshell (MSN) coating has been demonstrated as a versatile surface modification strategy for various kinds of inorganic functional nanoparticles, such as gold nanorods (GNRs), to achieve not only improved nanoparticle stability but also concomitant drug loading capability. However, limited drug loading capacity and low tumor accumulation rate in vivo are two major challenges for the biomedical applications of MSN-coated GNRs (GNR@MSN). In this study, by coating uniformly sized GNRs with MSN in an oil-water biphase reaction system, we have successfully synthesized a new bacteria-like GNR@MSN (i.e., bGNR@MSN) with a significantly enlarged pore size (4-8 nm) and surface area (470 m2/g). After PEGylation and highly efficient loading of doxorubicin (DOX, 40.9%, w/w), bGNR@MSN were used for positron emission tomography (PET, via facile and chelator-free 89Zr-labeling) and photoacoustic imaging-guided chemo-photothermal cancer therapy in vivo. PET imaging showed that 89Zr-labeled bGNR@MSN(DOX)-PEG can passively target to the 4T1 murine breast cancer-bearing mice with high efficiency (∼10 %ID/g), based on enhanced permeability and retention effect. Significantly enhanced chemo-photothermal combination therapy was also achieved due to excellent photothermal effect and near-infrared-light-triggered drug release by bGNR@MSN(DOX)-PEG at the tumor site. The promising results indicate great potential of bGNR@MSN-PEG nanoplatforms for future cancer diagnosis and therapy.
Project description:In this work, we report that gold nanorods coated with hydrophobically-modified mesoporous silica shells not only enhance photoacoustic (PA) signal over unmodified mesoporous silica coated gold nanorods, but that the relationship between PA amplitude and input laser fluence is strongly nonlinear. Mesoporous silica shells of ~14 nm thickness and with ~3 nm pores were grown on gold nanorods showing near infrared absorption. The silica was rendered hydrophobic with addition of dodecyltrichlorosilane, then re-suspended in aqueous media with a lipid monolayer. Analysis of the PA signal revealed not only an enhancement of PA signal compared to mesoporous silica coated gold nanorods at lower laser fluences, but also a nonlinear relationship between PA signal and laser fluence. We attribute each effect to the entrapment of solvent vapor in the mesopores: the vapor has both a larger expansion coefficient and thermal resistance than silica that enhances conversion to acoustic energy, and the hydrophobic porous surface is able to promote phase transition at the surface, leading to a nonlinear PA response even at fluences as low as 5 mJ cm-2. At 21 mJ cm-2, the highest laser fluence tested, the PA enhancement was >12-fold over mesoporous silica coated gold nanorods.