Effect of Substituents on the Photophysical Properties and Bioimaging Application of BODIPY Derivatives with Triphenylamine Substituents.

We investigated the intramolecular charge transfer characteristics in the S1 state of boron-dipyrromethene (BODIPY) derivatives with triphenylamine (TPA) substituents, depending on the substituted position and the number of substituents. Based on the spectroscopic and theoretical results, the ß-substitution of TPA on BODIPY hybridizes locally excited and intramolecular charge transfer characteristics in the S1 state because of strong coupling between the highest occupied molecular orbitals of BODIPY and TPA moieties, and consequently, the BODIPY derivatives with ß-substituted TPAs exhibit strong red-color fluorescence around 640 nm in nonpolar and moderately polar solvents. The TPA substituent with propeller-like nonplanar geometry could prevent H-type aggregation between neighboring BODIPY derivative units and induce aggregation-induced emission enhancement (AIEE) characteristics of the BODIPY derivatives with TPA substituents, which are helpful to maintain their emission efficiencies under highly concentrated and condensed conditions. Since the red-color emission and AIEE property of the BODIPY derivatives with ß-substituted TPAs are promising characteristics for a bioimaging application, we applied these derivatives to L-929 fibroblast cells for cellular imaging. The BODIPY derivative with a single ß-substituted TPA (compound 2) was effectively loaded into porous silica nanoparticles (SNPs). Consequently, we achieved good cellular uptake of 2-SNPs and good cellular imaging, which further confirmed the bioimaging ability of 2-SNPs.

Enhanced Photodynamic Anticancer Activities of Multifunctional Magnetic Nanoparticles (Fe3O4) Conjugated with Chlorin e6 and Folic Acid in Prostate and Breast Cancer Cells.

Photodynamic therapy (PDT) is a promising alternative to conventional cancer treatment methods. Nonetheless, improvement of in vivo light penetration and cancer cell-targeting efficiency remain major challenges in clinical photodynamic therapy. This study aimed to develop multifunctional magnetic nanoparticles conjugated with a photosensitizer (PS) and cancer-targeting molecules via a simple surface modification process for PDT. To selectively target cancer cells and PDT functionality, core magnetic (Fe3O4) nanoparticles were covalently bound with chlorin e6 (Ce6) as a PS and folic acid (FA). When irradiated with a 660-nm long-wavelength light source, the Fe3O4-Ce6-FA nanoparticles with good biocompatibility exerted marked anticancer effects via apoptosis, as confirmed by analyzing the translocation of the plasma membrane, nuclear fragmentation, activities of caspase-3/7 in prostate (PC-3) and breast (MCF-7) cancer cells. Ce6, used herein as a PS, is thus more useful for PDT because of its ability to produce a high singlet oxygen quantum yield, which is owed to deep penetration by virtue of its long-wavelength absorption band; however, further in vivo studies are required to verify its biological effects for clinical applications.

Aggregation-Induced Emission of Tetraphenylethene-Conjugated Phenanthrene Derivatives and Their Bio-Imaging Applications.

In this study, a series of rationally designed emissive phenanthrene derivatives were synthesized and their aggregation-induced emission (AIE) properties in tetrahydrofuran (THF)/water mixtures were investigated. Two tetraphenylethene (TPE) segments were conjugated to both ends of the phenanthrene core at the para-positions and meta-positions, resulting in pTPEP and mTPEP derivatives, respectively. While the TPE-conjugated phenanthrene derivatives did not show any emission when dissolved in pure THF, they showed strong sky-blue emissions in water-THF mixtures, which is attributed to the restriction of intramolecular motions of TPE segments by aggregation. Furthermore, silica nanoparticles loaded with these AIE-active compounds were prepared and proved to be promising intracellular imaging agents.

Functionalized ZnO Nanoparticles with Gallic Acid for Antioxidant and Antibacterial Activity against Methicillin-Resistant S. aureus.

In this study, we report a new multifunctional nanoparticle with antioxidative and antibacterial activities in vitro. ZnO@GA nanoparticles were fabricated by coordinated covalent bonding of the antioxidant gallic acid (GA) on the surface of ZnO nanoparticles. This addition imparts both antioxidant activity and high affinity for the bacterial cell membrane. Antioxidative activities at various concentrations were evaluated using a 2,2'-azino-bis(ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging method. Antibacterial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus: S. aureus), including several strains of methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria (Escherichia coli). The functionalized ZnO@GA nanoparticles showed good antioxidative activity (69.71%), and the bactericidal activity of these nanoparticles was also increased compared to that of non-functionalized ZnO nanoparticles, with particularly effective inhibition and high selectivity for MRSA strains. The results indicate that multifunctional ZnO nanoparticles conjugated to GA molecules via a simple surface modification process displaying both antioxidant and antibacterial activity, suggesting a possibility to use it as an antibacterial agent for removing MRSA.

Optimized Photodynamic Therapy with Multifunctional Cobalt Magnetic Nanoparticles.

Photodynamic therapy (PDT) has been adopted as a minimally invasive approach for the localized treatment of superficial tumors, representing an improvement in the care of cancer patients. To improve the efficacy of PDT, it is important to first select an optimized nanocarrier and determine the influence of light parameters on the photosensitizing agent. In particular, much more knowledge concerning the importance of fluence and exposure time is required to gain a better understanding of the photodynamic efficacy. In the present study, we synthesized novel folic acid-(FA) and hematoporphyrin (HP)-conjugated multifunctional magnetic nanoparticles (CoFe2O4-HPs-FAs), which were characterized as effective anticancer reagents for PDT, and evaluated the influence of incubation time and light exposure time on the photodynamic anticancer activities of CoFe2O4-HPs-FAs in prostate cancer cells (PC-3 cells). The results indicated that the same fluence at different exposure times resulted in changes in the anticancer activities on PC-3 cells as well as in reactive oxygen species formation. In addition, an increase of the fluence showed an improvement for cell photo-inactivation. Therefore, we have established optimized conditions for new multifunctional magnetic nanoparticles with direct application for improving PDT for cancer patients.

Antioxidant Potential and Antibacterial Efficiency of Caffeic Acid-Functionalized ZnO Nanoparticles.

We report a novel zinc oxide (ZnO) nanoparticle with antioxidant properties, prepared by immobilizing the antioxidant 3-(3,4-dihydroxyphenyl)-2-propenoic acid (caffeic acid, CA) on the surfaces of micro-dielectric barrier discharge (DBD) plasma-treated ZnO nanoparticles. The microstructure and physical properties of ZnO@CA nanoparticles were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), infrared spectroscopy, and steady state spectroscopic methods. The antioxidant activity of ZnO@CA nanoparticles was evaluated using an ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation decolorization assay. ZnO@CA nanoparticles exhibited robust antioxidant activity. Moreover, ZnO@CA nanoparticles showed strong antibacterial activity against Gram-positive bacteria (Staphylococcus aureus) including resistant bacteria such as methicillin-resistant S. aureus and against Gram-negative bacteria (Escherichia coli). Although Gram-negative bacteria appeared to be more resistant to ZnO@CA nanoparticles than Gram-positive bacteria, the antibacterial activity of ZnO@CA nanoparticles was dependent on particle concentration. The antioxidant and antibacterial activity of ZnO@CA may be useful for various biomedical and nanoindustrial applications.

In Situ Forming and H2O2-Releasing Hydrogels for Treatment of Drug-Resistant Bacterial Infections.

Various types of commercialized wound dressings (e.g., films, foams, gels, and nanofiber meshes) have been clinically used as a physical barrier against bacterial invasion and as wound-healing materials. Although these dressings can protect the wounded tissue from the external environment, they cannot treat the wounds that are already infected with bacteria. Herein, we report in situ H2O2-releasing hydrogels as an active wound dressing with antibacterial properties for treatment of drug-resistant bacterial infection. In this study, H2O2 was used for two major purposes: (1) in situ gel formation via a horseradish peroxidase (HRP)/H2O2-triggered cross-linking reaction, and (2) antibacterial activity of the hydrogel via its oxidative effects. We found that there were residual H2O2 in the matrix after in situ HRP-catalyzed gelling, and varying the feed amount of H2O2 (1-10 mM; used to make hydrogels) enabled control of H2O2 release kinetics within a range of 2-509 µM. In addition, although the gelatin-hydroxyphenyl propionic acid (GH) gel called "GH 10" (showing the greatest H2O2 release, 509 µM) slightly decreased cell viability (to 82-84%) of keratinocyte (HaCaT) and fibroblast (L-929) cells in in vitro assays, none of the hydrogels showed significant cytotoxicity toward tissues in in vivo skin irritation tests. When the H2O2-releasing hydrogels that promote in vivo wound healing, were applied to various bacterial strains in vitro and ex vivo, they showed strong killing efficiency toward Gram-positive bacteria including Staphylococcus aureus, S. epidermidis, and clinical isolate of methicillin-resistant S. aureus (MRSA, drug-resistant bacteria), where the antimicrobial effect was dependent on the concentration of the H2O2 released. The present study suggests that our hydrogels have great potential as an injectable/sprayable antimicrobial dressing with biocompatibility and antibacterial activity against drug-resistant bacteria including MRSA for wound and infection treatment.

Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells.

In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe2O4) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe2O4 particles were finely adjusted by controlling the size of the primary CoFe2O4 nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe2O4-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe2O4-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe2O4-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism.

Facile Synthesis of Photofunctional Nanolayer Coatings on Titanium Substrates.

We developed a two-step chemical bonding process using photosensitizer molecules to fabricate photofunctional nanolayer coatings on hematoporphyrin- (HP-) coated Ti substrates. In the first step, 3-aminopropyltriethoxysilane was covalently functionalized onto the surface of the Ti substrates to provide heterogeneous sites for immobilizing the HP molecules. Then, HP molecules with carboxyl groups were chemically attached to the amine-terminated nanolayer coatings via a carbodiimide coupling reaction. The microstructure and elemental and phase composition of the HP-coated Ti substrates were investigated using field-emission scanning electron microscopy and energy-dispersive X-ray spectrometry. The photophysical properties of the photofunctional nanolayer coatings were confirmed using reflectance ultraviolet-visible absorption and emission spectrophotometry. The singlet oxygen generation efficiency of the photofunctional nanolayer coatings was determined using the decomposition reaction of 1,3-diphenylisobenzofuran. The HP-coated Ti substrates exhibited good biocompatibility without any cytotoxicity, and these nanolayer coatings generated singlet oxygen, which can kill microorganisms using only visible light.

Photodynamic Anticancer Activities of Multifunctional Cobalt Ferrite Nanoparticles in Various Cancer Cells.

To develop novel multifunctional magnetic nanoparticles (MNPs) with good magnetic properties, biocompatibility, and anticancer activities by photodynamic therapy (PDT), we synthesized multifunctional cobalt ferrite (CoFe2O4) nanoparticles (CoFe2O4-HPs-FAs) functionalized by coating them with hematoporphyrin (HP) for introducing photo-functionality and by conjugating with folic acid (FA) for targeting cancer cells. We evaluated the activities of the CoFe2O4-HPs-FAs by checking magnetic resonance imaging (MRI) in vitro, its biocompatibility, and photodynamic anticancer activities on FA receptor (FR)-positive and FR-negative cancer cell lines, Hela, KB, MCF-7, and PC-3 cells, to use for clinical applications. In this study, we have demonstrated that the CoFe2O4-HPs-FAs have good MRI and biocompatibility with non-cytotoxicity, and remarkable photodynamic anticancer activities at very low concentrations regardless of cell types. Particularly, the photo-killing abilities in 3.13 µg/mL of CoFe2O4-HPs-FAs were measured to be 91.8% (p < 0.002) for Hela, 94.5% (p < 0.007) for KB, 79.1% (p < 0.003) for MCF-7, and 71.3% (p < 0.006) for PC-3. The photodynamic anticancer activities in 6.25 and 12.5 µg/mL of CoFe2O4-HPs-FAs were measured to be over 95% (p < 0.004) to almost 100% regardless of cell types. The newly developed multifunctional CoFe2O4-HPs-FAs are effective for PDT and have potential as therapeutic agents for MRI-based PDT, because they have a high saturation value of magnetization and superparamagnetism.

Functional manipulation of dendritic cells by photoswitchable generation of intracellular reactive oxygen species.

Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the generation of intracellular ROS and examine their specific role in activating dendritic cells (DCs). Photoswitchable generation of intracellular ROS rapidly induced cytosolic mobilization of Ca(2+), differential activation of mitogen-activated protein kinases, and nuclear translocation of NF-κB. Moreover, a transient intracellular ROS surge could activate immature DCs to mature and potently enhance migration in vitro and in vivo. Finally, we observed that intracellular ROS-stimulated DCs enhanced antigen specific T-cell responses in vitro and in vivo, which led to delayed tumor growth and prolonged survival of tumor-bearing mice when immunized with a specific tumor antigen. Therefore, a transient intracellular ROS surge alone, if properly manipulated, can cause immature DCs to differentiate into a motile state and mature forms that are sufficient to initiate adaptive T cell responses in vivo.

Photodynamic Anticancer Activity of CoFe2O4 Nanoparticles Conjugated with Hematoporphyrin.

This work reports the synthesis and the characterization of water-soluble and biocompatible photosensitizer (PS)-conjugated magnetic nanoparticles composed of a cobalt ferrite (CoFe2O4) magnetic core coated with a biocompatible hematoporphyrin (HP) shell. The photo-functional cobalt ferrite magnetic nanoparticles (CoFe2O4@HP) were uniform in size, stable against PS leaching, and highly efficient in the photo-generation of cytotoxic singlet oxygen under visible light. With the CoFe2O4@HP, we acquired in vitro MR images of cancer cells (PC-3) and confirmed good biocompatibility of the CoFe2O4@HP in both normal and cancer cells. In addition, we confirmed the potential of the CoFe2O4@HP as an agent for photodynamic therapy (PDT) applications. The photodynamic anticancer activities in 25, 50, and 100 µg/mL of CoFe2O4@HP were measured and found to exceed 99% (99.0, 99.4, and 99.5%) (p < 0.002). The photodynamic anticancer activity was 81.8% (p < 0.003). From these results, we suggest that our CoFe2O4@HP can be used safely as a type of photodynamic cancer therapy with potential as a therapeutic agent having good biocompatibility. Moreover, these photo-functional magnetic nanoparticles are highly promising for applications in versatile imaging diagnosis and as a therapy tool in biomedical engineering.

Size dependent photocatalytic activity of photofunctional magnetic core-shell (Fe3O4@TiO2) particles.

The development and enlargement of addressable magnetic core-shell hetero-architectures in a simple and economic way still remain a synthetic challenge. Herein, photofunctional magnetic FT1 (Fe3O4@TiO2 particles with 120 nm size) and FT4 ((Fe3O4@TiO2 particles with 420 nm size) core-shell particles with controlled size were fabricated successfully via a simple surface modification process that induces the atomic layer deposition (ALD) method. The size control of photofunctional magnetic particles has been adjusted by controlling the ratio of V(EG)/V(DEG) during the solvothermal reaction. Photocatalytic ability examination of the FT1 and FT4 core-shell particles was carried out in Rhodamine B (RhB) solutions illuminated under Xe light in a photochemical reactor. The photocatalytic activity depending on particle size indicates that the small FT1 particles are superior to the large FT4 particles due to the large surface area.

Photosensitizer and vancomycin-conjugated novel multifunctional magnetic particles as photoinactivation agents for selective killing of pathogenic bacteria.

Novel multifunctional magnetic particles (MMPs) conjugated with photosensitizer and vancomycin were fabricated by surface modification of Fe(3)O(4) particles. The capacities to target, capture and inactivate pathogenic bacteria and good biocompatibility suggest that the MMPs have great potentials as photodynamic inactivation agents for serious bacterial contamination.

Self-assembly of nanosized 0D clusters: CdS quantum dot-polyoxotungstate nanohybrids with strongly coupled electronic structures and visible-light-active photofunctions.

Nanohybrids of CdS-polyoxotungstate with strongly coupled electronic structures and visible-light-active photofunctions can be synthesized by electrostatically derived self-assembly of very small CdS quantum dots, or QDs, (particle size ≈ 2.5 nm) and polyoxotungstate nanoclusters (cluster size ≈1 nm). The formation of CdS-polyoxotungstate nanohybrids is confirmed by high-resolution transmission electron microscopy, elemental mapping, and powder X-ray diffraction analysis. Due to the strong electronic coupling between two semiconductors, the CdS-polyoxotungstate nanohybrids show a narrow bandgap energy of around 1.9-2.7 eV, thus reflecting their ability to harvest visible light. Time-resolved photoluminescence experiments indicate that the self-assembly between nanosized CdS and polyoxotungstate is very effective in increasing the lifetime of holes and electrons, thus indicating an efficient electron transfer between two-component semiconductors. The hybridization results not only in a significant improvement in the photostability of CdS QD but also in the creation of visible-light-induced photochromism. Of particular importance is that the present nanohybrids show visible-light-driven photocatalytic activity to produce H(2) and O(2) , which is superior to those of the unhybridized CdS and polyoxotungstate. The self-assembly of nanometer-level semiconductor clusters can provide a powerful way of optimizing the photoinduced functionalities of each component (i.e., visible-induced photochromism and photocatalysis) by means of strong electronic coupling.

Fabrication of mesoporous titania membrane of dual-pore system and its photocatalytic activity and dye-sensitized solar cell performance.

We report the fabrication of a novel titania membrane of the dual-pore system that is strategically designed and prepared by a two-step replication process and sol-gel reaction. The primary nanoporous channel structure is fabricated by the cage-like PMMA template (CPT) obtained from the nanoporous alumina membrane and the secondary mesoporous structure is formed by the sol-gel reaction of the lyotropic precursor solution within the CPT. Furthermore the mesoporous titania membrane (MTM) frame consists of the titania nanoparticles of 10-12 nm in diameter. Morphology and structural properties of the MTM are investigated by field emission scanning electron microscopy, high resolution transmission electron microscopy, x-ray diffraction and Brunauer-Emmett-Teller surface area. The photocatalytic activity and the solar energy properties of the MTM are characterized by UV-vis spectrophotometer, spectrofluorometer and photoinduced I-V measurement. The photocatalytic test indicates that the MTM has higher efficiency than the commercial P25 with a good recyclability due to its large-scale membrane style and the preliminary result on the solar cell application shows a solar energy conversion efficiency of 3.35% for the dye-sensitized solar cell utilizing the MTM.

Photophysical properties and energy transfer pathway of Er(III) complexes with Pt-porphyrin and terpyridine ligands.

The photophysical properties of Er(III) complexes coordinated with platinum[5,10,15-triphenyl-20-(4-carboxyphenyl)-porphyrin] (PtP) and terpyridine (tpy) ligands in organic solution were investigated. The Er(III) complex emitted sensitized near-IR (NIR) luminescence when the PtP ligands were excited under deoxygenated conditions. The quantum yield (PhiLn) of the sensitized luminescence was 0.015%, as evaluated from luminescence lifetime. The photophysical studies and theoretical calculations suggest that the Förster resonance mechanism is very suitable for the energy transfer from PtP to the Er(III) ion and occurred through the first triplet excited state of PtP. The 12.3% energy transfer from the triplet state to the 4F9/2 and 4I9/2 states of Er(III) occurred with a rate distribution of 3.36x10(5) and 6.67x10(4) s(-1), respectively. In addition, the observed triplet quantum yield of the PtP ligand in [Ln(PtP)3(tpy)] proved that the energy transfer from the singlet excited state of the PtP ligand to the Er(III) ion did not take place.