RESUMO
Near-infrared (NIR)-induced dye-based theranostic drug delivery carriers are used for critical image-guided chemo-photothermal cancer therapy. However, most carriers fail to deliver sufficient heat and fluorescence efficiently due to direct π-π stacking of the aromatic rings of the NIR dye and drug. In the work reported herein, we examined a self-assembled heptamethine cyanine dye dimer (CyD) with improved heat and fluorescence delivery that was developed by manipulating the unique structural and optical properties of the dimer. The H-aggregation of CyD in an aqueous solution generated a great amount of heat by transforming the energy of the excited electrons into non-radiative energy. Moreover, the disulfide bond of CyD assisted nanoparticles with a drug by minimizing the interaction between the NIR dye and drug, and also by releasing the drug in a redox environment. As a result, DOX encapsulated within CyD (CyD/DOX) showed strong heat generation and fluorescence imaging in tumor-bearing mice, allowing detection of the tumor site and inhibition of tumor growth by chemo-photothermal therapy. The multiplicity of features supplied by the newly developed CyD demonstrated the potential of CyD/DOX as an NIR dye-based theranostic drug-delivery carrier for effective chemo-photothermal cancer therapy.
Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Camundongos , Fototerapia , Medicina de Precisão , Nanomedicina TeranósticaRESUMO
The strategy of co-loading therapeutic agents in a single nanocarrier is the most common method in theranostic cancer research. However, it is still challenging to encapsulate theranostic agents that have different physicochemical properties in a single nanocarrier system because of the immiscibility between the hydrophobic fluorescent molecule and the hydrophilic drug molecule. Thus, we report a novel concept of a theranostic nanoparticle (NP) consisting of an amphiphilic near-infrared (NIR) dye as a hydrophilic drug delivery carrier with enhanced NIR imaging capability. Unlike conventional nanocarrier systems, the newly designed amphiphilic NIR dyes (Cy-C dyes) function as both the drug delivery carrier and the fluorescent imaging agent. It can be utilized for therapy and diagnosis simultaneously by simply encapsulating the hydrophilic drug. This method is innovative not only due to formation of the theranostic nanoparticle for immiscible hydrophilic drug delivery but also because of generation of strong fluorescence signals due to the Cy-C dyes on the surfaces of the NPs. In this study, Cy-C (C = C3, C6, and C9) dyes were designed by conjugating the heptamethine cyanine dye with poly(ethylene glycol) (PEG5K) and polyethyleneimine 2000 (PEI2K). The result was self-assembled structures that effectively encapsulated a hydrophilic drug molecule (MTX) without self-quenching and scattered light interference. Among the Cy-C NPs encapsulating MTX (Cy-C/MTX NPs), Cy-C6/MTX and Cy-C9/MTX formed a concentric supramolecular bilayer (like liposomes in aqueous solution) and were capable of translocating hydrophilic drug molecules to their aqueous interior spaces. The supramolecular bilayer structure of Cy-C9/MTX provides better particle stability and drug delivery efficacy than does the supramolecular monolayer structure of Cy-C3/MTX. In addition, Cy-C9/MTX demonstrated excellent blood circulation and long-term tumor retention qualities in living mice. The effective tumor suppression ability of Cy-C9/MTX validated the concept that the amphiphilic Cy-C9 dye is the best nanoplatform for theranostics based on hydrophilic drug delivery.
Assuntos
Nanopartículas , Medicina de Precisão , Animais , Portadores de Fármacos , Corantes Fluorescentes , Interações Hidrofóbicas e Hidrofílicas , CamundongosRESUMO
In this research, various processing conditions were implemented to enhance the mechanical properties of Al-Si alloys. The silicon content was varied from hypoeutectic (Si-10 wt.%) to eutectic (Si-12.6 wt.%) and hypereutectic (Si-14 wt.%) for the preparation of Al-XSi-3Cu-0.5Fe-0.6 Mg (X = 10â»14%) alloys using die casting. Subsequently, these alloys were hot-extruded with an optimum extrusion ratio (17:1) at 400 °C to match the output extruded bar to the compressor size. An analysis of the microstructural features along with a chemical compositional analysis were carried out using scanning electron microscope along with energy dispersive X-ray spectroscopy and transmission electron microscope. The SEM micrographs of the extruded samples displayed cracks in primary Si, and the intermetallic (ß-Al5FeSi) phase was fragmented accordingly. In addition, the silicon phase was homogenously distributed, and the size remained constant. The mechanical properties of the extruded samples were enhanced by the increase of silicon content, and consequently the ductility decreased. By implementing proper T6 heat treatment parameters, coherent Al2Cu phases were formed in the Al matrix, and the Si phase was gradually increased along with the silicon content. Therefore, high tensile strength was achieved, reaching values for the Al-XSi-3Cu-0.5Fe-0.6Mg (X = 10â»14%) alloys of 366 MPa, 388 MPa, and 420 MPa, respectively.
RESUMO
A noninvasive and selective therapy, photodynamic therapy (PDT) is widely researched in clinical fields; however, the lower efficiency of PDT can induce unexpected side effects. Mitochondria are extensively researched as target sites to maximize PDT effects because they play crucial roles in metabolism and can be used as cancer markers due to their high transmembrane potential. Here, a mitochondria targeting photodynamic therapeutic agent (MitDt) is developed. This photosensitizer is synthesized from heptamethine cyanine dyes, which are conjugated or modified as follows. The heptamethine meso-position is conjugated with a triphenylphosphonium derivative for mitochondrial targeting, the N-alkyl side chain is modified for regulation of charge balance and solubility, and the indolenine groups are brominated to enhance reactive oxygen species generation (ROS) after laser irradiation. The synthesized MitDt increases the cancer uptake efficiency due to the lipo-cationic properties of the triphenylphosphonium, and the PDT effects of MitDt are amplified after laser irradiation because mitochondria are susceptible to ROS, the response to which triggers an apoptotic anticancer effect. Consequently, these hypotheses are demonstrated by in vitro and in vivo studies, and the results indicate strong potential for use of MitDts as efficient single-molecule-based PDT agents for cancer treatment.
RESUMO
This study investigates the performance of single-crystalline nanomaterials of wide-band gap naphthalene diimide (NDI) derivatives with methylene-bridged aromatic side chains. Such materials are found to be easily used as high-performance, visible-blind near-UV light detectors. NDI single-crystalline nanoribbons are assembled using a simple solution-based process (without solvent-inclusion problems), which is then applied to organic phototransistors (OPTs). Such OPTs exhibit excellent n-channel transistor characteristics, including an average electron mobility of 1.7 cm2 V-1 s-1, sensitive UV detection properties with a detection limit of â¼1 µW cm-2, millisecond-level responses, and detectivity as high as 1015 Jones, demonstrating the highly sensitive organic visible-blind UV detectors. The high performance of our OPTs originates from the large face-to-face π-π stacking area between the NDI semiconducting cores, which is facilitated by methylene-bridged aromatic side chains. Interestingly, NDI-based nanoribbon OPTs exhibit a distinct visible-blind near-UV detection with an identical detection limit, even under intense visible light illumination (for example, 104 times higher intensity than UV light intensity). Our findings demonstrate that wide-band gap NDI-based nanomaterials are highly promising for developing high-performance visible-blind UV photodetectors. Such photodetectors could potentially be used for various applications including environmental and health-monitoring systems.
RESUMO
A series of fluorescent molecular rotors obtained by introducing two rotational groups ("rotators"), which exhibit different rotational and electron-donating abilities, are discussed. Whereas the control molecular rotor, PH, includes a single rotator (the widely used phenyl group), the PO molecular rotors consist of two rotators (a phenyl group and an alkoxy group), which exhibit simultaneous strongly electron-donating and easy rotational abilities. Compared with the control rotor PH, PO molecular rotors exhibited one order of magnitude higher quantum yield (fluorescence intensity) and simultaneously exhibited significantly higher fluorescence contrast. These properties are directly related to the strong electron-donating ability and low energy barrier of rotation of the alkoxy group, as confirmed by dynamic fluorescence experiments and quantum chemical calculations. The PO molecular rotors exhibited two fluorescence relaxation pathways, whereas the PH molecular rotor exhibited a single fluorescence relaxation pathway. Cellular fluorescence imaging with PO molecular rotors for mapping cellular viscosity was successfully demonstrated.
RESUMO
Highly efficient nonlinear optical organic crystals are very attractive for various photonic applications including terahertz (THz) wave generation. Up to now, only two classes of ionic crystals based on either pyridinium or quinolinium with extremely large macroscopic optical nonlinearity have been developed. This study reports on a new class of organic nonlinear optical crystals introducing electron-accepting benzothiazolium, which exhibit higher electron-withdrawing strength than pyridinium and quinolinium in benchmark crystals. The benzothiazolium crystals consisting of new acentric core HMB (2-(4-hydroxy-3-methoxystyryl)-3-methylbenzo[d]thiazol-3-ium) exhibit extremely large macroscopic optical nonlinearity with optimal molecular ordering for maximizing the diagonal second-order nonlinearity. HMB-based single crystals prepared by simple cleaving method satisfy all required crystal characteristics for intense THz wave generation such as large crystal size with parallel surfaces, moderate thickness and high optical quality with large optical transparency range (580-1620 nm). Optical rectification of 35 fs pulses at the technologically very important wavelength of 800 nm in 0.26 mm thick HMB crystal leads to one order of magnitude higher THz wave generation efficiency with remarkably broader bandwidth compared to standard inorganic 0.5 mm thick ZnTe crystal. Therefore, newly developed HMB crystals introducing benzothiazolium with extremely large macroscopic optical nonlinearity are very promising materials for intense broadband THz wave generation and other nonlinear optical applications.
RESUMO
Cell-penetrating peptides (CPPs) have been widely used to deliver nucleic acid molecules. Generally, CPPs consisting of short amino acid sequences have a linear structure, resulting in a weak complexation and low transfection efficacy. To overcome these drawbacks, a novel type of CPP is required to enhance the delivery efficacy while maintaining its safe use at the same time. Herein, we report that a bioreducible branched poly-CPP structure capable of responding to reducing conditions attained both outstanding delivery effectiveness and selective gene release in carcinoma cells. Branched structures provide unusually strong electrostatic attraction between DNA and siRNA molecules, thereby improving the transfection capability through a tightly condensed form. We designed a modified type of nona-arginine (mR9) and synthesized a branched-mR9 (B-mR9) using disulfide bonds. A novel B-mR9/pDNA polyplex exhibited redox-cleavability and high transfection efficacy compared to conventional CPPs, with higher cell viability as well. B-mR9/VEGF siRNA polyplex exhibited significant serum stability and high gene-silencing effects in vitro. Furthermore, the B-mR9 polyplex showed outstanding tumor accumulation and inhibition ability in vivo. The results suggest that the bioreducible branched poly CPP has great potential as a gene delivery platform.
Assuntos
Arginina/análogos & derivados , Peptídeos Penetradores de Células/química , DNA/administração & dosagem , Técnicas de Transferência de Genes , Plasmídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Sobrevivência Celular , DNA/genética , Feminino , Células HEK293 , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Plasmídeos/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transfecção , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Cell penetrating peptides (CPPs) as one class of non-viral vectors, have been widely explored as a delivery tool due to their cell-penetrating capability with low cytotoxicity. However, CPPs have reported to have low gene transfection efficiency mainly due to the fact that DNA is larger than other biomolecules. On the other hand, the conventional linear CPPs are unstable for constructing the DNA complexes with it. Thus, here we designed a branched CPP using disulfide bridges based on the linear TAT peptide, to enhance the gene delivery efficiency in a better way. RESULTS: The branched TAT (BTAT) was synthesized by the DMSO oxidation method and showed high-molecular-weight about 294 kDa. The resulting BTAT was complexed with plasmid green fluorescence protein (pGFP) gene at various N/P ratios. The gene transfection efficiency was assessed on HeLa cells after treating with BTAT/pGFP complexes, showed high gene transfection efficiency as conformed by flowcytometry followed by confocal laser scanning microscopy (CLSM) visualization. CONCLUSION: The novel BTAT/pGFP complex exhibited significantly higher stability and redox cleavability by reducing agent. In addition, BTAT showed higher transfection efficiency approximately 40-fold than those of the TAT and mTAT complexes. Our primary experiments demonstrated the potential of BTAT as a suitable candidate for gene delivery and it could be applied for various types of gene delivery platforms.