Reversible and Sensitive Hg2+ Detection by a Cell-Permeable Ytterbium Complex.

A cell-permeable ytterbium complex shows reversible binding with Hg2+ in aqueous solution and in vitroby off-on visible and NIR emission. The fast response and 150 nM sensitivity of Hg2+ detection is based upon FRET and the lanthanide antenna effect. The reversible Hg2+ detection can be performed in vitro, and the binding mechanism is suggested by NMR employing the motif structure in a La complex and by DFT calculations.

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent.

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional--PDT and imaging--gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species--singlet oxygen--before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of "precision medicine" in line with stem cell and gene therapies as tools in cancer therapy.

Gallium and Functionalized-Porphyrins Combine to Form Potential Lysosome-Specific Multimodal Bioprobes.

A water-soluble bimetallic normal ("cold") and radiochemical ("hot") gallium-porphyrin-ruthenium-bipyridine complex (GaporRu-1) has been synthesized by microwave methodology in short reaction times with good (>85%) yields. (68)GaporRu-1 is demonstrated to be a potential multimodal and functional bioprobe for positron emission tomography (PET), lysosome specific optical imaging, and photodynamic therapy.

Highly selective and responsive visible to near-IR ytterbium emissive probe for monitoring mercury(II).

A new lanthanide probe based on the fluorescence resonance energy transfer (FRET) process with the combination of ytterbium porphyrinate complex and a rhodamine B derivative unit was synthesized to detect the Hg(2+) ion with responsive emission in the visible and near-IR region with a detection limit of 10 µM.

Monitoring and inhibition of Plk1: amphiphilic porphyrin conjugated Plk1 specific peptides for its imaging and anti-tumor function.

Polo-like kinase 1 (Plk1) is well-known for taking part in cell cycle progression and regulation. Using small molecules for Plk inhibition has been well documented in the literature. However, there are several intrinsic and intractable problems associated with this approach. For example monitoring small molecule Plk inhibitors as anti-tumor agents in vitro/in vivo is often ineffective, they can have poor cell internalization and be susceptible to enzymatic degradation. Herein, we report the synthesis of cell-permeable, water-soluble amphiphilic porphyrin ­ Plk1 specific peptide bioconjugates, Por-P1 and Por-P2. In addition to resolving the aforementioned problems of the small molecule inhibitors Por-P2 manifests responsive emission enhancement upon binding with Plk1 in aqueous medium and in vitro, while potently triggering G2-M phase arrest and then apoptosis selectively in the cancer cells tested. In combination our findings make Por-P2 a promising candidate for the preparation of a new generation of smart chemotherapeutic targeting agents (imaging and inhibition) for Plk1 in particular cancer cell lines.

Comparative studies of the cellular uptake, subcellular localization, and cytotoxic and phototoxic antitumor properties of ruthenium(II)-porphyrin conjugates with different linkers.

Six water-soluble free-base porphyrin-Ru(II) conjugates, 1-3, and Zn(II) porphyrin-Ru(II) conjugates, 4-6, with different linkers between the hydrophobic porphyrin moiety and the hydrophilic Ru(II)-polypyridyl complex, have been synthesized. The linear and two-photon-induced photophysical properties of these conjugates were measured and evaluated for their potential application as dual in vitro imaging and photodynamic therapeutic (PDT) agents. Conjugates 1-3, with their high luminescence and singlet oxygen quantum yields, were selected for further study of their cellular uptake, subcellular localization, and cytotoxic and photocytotoxic (under linear and two-photon excitation) properties using HeLa cells. Conjugate 2, with its hydrophobic phenylethynyl linker, was shown to be highly promising for further development as a bifunctional probe for two-photon (NIR) induced PDT and in vitro imaging. Cellular uptake and subcellular localization properties were shown to be crucial to its PDT efficacy.

Plasmonic enhancement and polarization dependence of nonlinear upconversion emissions from single gold nanorod@SiO2@CaF2:Yb3+,Er3+ hybrid core-shell-satellite nanostructures.

Lanthanide-doped upconversion nanocrystals (UCNCs) have recently become an attractive nonlinear fluorescence material for use in bioimaging because of their tunable spectral characteristics and exceptional photostability. Plasmonic materials are often introduced into the vicinity of UCNCs to increase their emission intensity by means of enlarging the absorption cross-section and accelerating the radiative decay rate. Moreover, plasmonic nanostructures (e.g., gold nanorods, GNRs) can also influence the polarization state of the UC fluorescence-an effect that is of fundamental importance for fluorescence polarization-based imaging methods yet has not been discussed previously. To study this effect, we synthesized GNR@SiO2@CaF2:Yb3+,Er3+ hybrid core-shell-satellite nanostructures with precise control over the thickness of the SiO2 shell. We evaluated the shell thickness-dependent plasmonic enhancement of the emission intensity in ensemble and studied the plasmonic modulation of the emission polarization at the single-particle level. The hybrid plasmonic UC nanostructures with an optimal shell thickness exhibit an improved bioimaging performance compared with bare UCNCs, and we observed a polarized nature of the light at both UC emission bands, which stems from the relationship between the excitation polarization and GNR orientation. We used electrodynamic simulations combined with Förster resonance energy transfer theory to fully explain the observed effect. Our results provide extensive insights into how the coherent interaction between the emission dipoles of UCNCs and the plasmonic dipoles of the GNR determines the emission polarization state in various situations and thus open the way to the accurate control of the UC emission anisotropy for a wide range of bioimaging and biosensing applications.

A luminescent lanthanide approach towards direct visualization of primary cilia in living cells.

We report a direct imaging tool, HGEu001, for primary cilia in living cells, which is specific, and based on the UV light or near infrared laser (via two-photon excitation) induced long-lived europium luminescence.

αvß3-Isoform specific erbium complexes highly specific for bladder cancer imaging and photodynamic therapy.

We have synthesized a bifunctional erbium-porphyrin tumor imaging and PDT agent (Er-R3) that is capable of killing bladder cancer cells via its selective binding to the integrin αvß3 isoform overexpressed on the cell membrane.

Gadolinium and Platinum in Tandem: Real-time Multi-Modal Monitoring of Drug Delivery by MRI and Fluorescence Imaging.

A novel dual-imaging cisplatin-carrying molecular cargo capable of performing simultaneous optical and MR imaging is reported herein. This long-lasting MRI contrast agent (r1 relaxivity of 23.4 mM-1s-1 at 3T, 25 oC) is a photo-activated cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer efficacy by MRI with a much longer retention time (24 hours) in several organs such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent MRI analyses of therapy efficacy within its reasonably short clearance time of 4 hours. There is also responsive fluorescence enhancement for monitoring by photon-excitation.

A Smart Europium-Ruthenium Complex as Anticancer Prodrug: Controllable Drug Release and Real-Time Monitoring under Different Light Excitations.

A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. Under evaluation-window irradiation (λirr = one-photon 350 nm or two-photon 700 nm), the drug delivery process can be quantitatively monitored in real-time because of the long-lived red europium emission. Linear relationships between released drug concentration and ESI-MS or luminescence responses are established. Finally, the efficiency of the new prodrug is demonstrated both in vitro RuEuL anticancer prodrug over some existing ones and open the way for decisive improvements in multipurpose prodrugs.

Room temperature molecular up conversion in solution.

Up conversion is an Anti-Stokes luminescent process by which photons of low energy are piled up to generate light at a higher energy. Here we show that the addition of fluoride anions to a D2O solution of a macrocyclic erbium complex leads to the formation of a supramolecular [(ErL)2F](+) assembly in which fluoride is sandwiched between two complexes, held together by the synergistic interactions of the Er-F-Er bridging bond, four intercomplex hydrogen bonds and two aromatic stacking interactions. Room temperature excitation into the Er absorption bands at 980 nm of a solution of the complex in D2O results in the observation of up converted emission at 525, 550 and 650 nm attributed to Er centred transitions via a two-step excitation. The up conversion signal is dramatically increased upon formation of the [(ErL)2F](+) dimer in the presence of 0.5 equivalents of fluoride anions.

Urinary Polyamines: A Pilot Study on Their Roles as Prostate Cancer Detection Biomarkers.

Current screening methods towards prostate cancer (PCa) are not without limitations. Research work has been on-going to assess if there are other better tests suitable for primary or secondary screening of PCa to supplement the serum prostate specific antigen (PSA) test, which fails to work accurately in a grey zone of 4-10ng/ml. In this pilot study, the potential roles of urinary polyamines as prostate cancer biomarkers were evaluated. PCa, benign prostatic hyperplasia (BPH) patients and healthy controls (HC) showing PSA>4.0ng/ml were enrolled in the study. Their urine samples were obtained, and the urinary levels of putrescine (Put), spermidine (Spd) and spermine (Spm) were determined by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS). Receiver operating characteristics (ROC) curve and Student's t-test were used to evaluate their diagnostic accuracies. Among the three biogenic polyamines, Spm had demonstrated a good diagnostic performance when comparing their levels in PCa patients with BPH patients (1.47 in PCa vs 5.87 in BPH; p<0.0001). Results are in accordance with transrectal ultrasound prostatic biopsy (TRUSPB) results, with an area under curve (AUC) value of 0.83±0.03. Therefore urinary Spm shows potential to serve as a novel PCa diagnostic biomarker, which in turn can help to address the limited sensitivity and specificity problem of serum PSA test.

pH-Dependent Cancer-Directed Photodynamic Therapy by a Water-Soluble Graphitic-Phase Carbon Nitride-Porphyrin Nanoprobe.

Theranostic photodynamic nanomaterials suffer from poor water solubility and nontargeted toxicity. A water-soluble graphitic-phase carbon nitride-based material (g-C3 N4 ) conjugated to a positively charged porphyrin P2 (conjugating concentration: 60 µm mg-1 mL-1 ) is shown to be a new concept of photodynamic therapeutic agent (g-C3 N4 -P2). The pH-sensitive emission of g-C3 N4 is the driving force for the generation of 1 O2 from g-C3 N4 -P2. The amount of 1 O2 /light generated from a photosensitizer porphyrin can be controlled by the pH-sensitive emission of g-C3 N4 at acidic pH (pH 4-6), especially under acidic conditions mimicking those of tumor tissue, and thus has the potential to be utilized as a cancer-selective PDT agent.

Ultrabright Lanthanide Nanoparticles.

Invited for this month's cover are the collaborating groups of Dr. Loïc J. Charbonnière at CNRS/Université de Strasbourg, France and Dr. Ka-Leung Wong at Hong Kong Baptist University, Hong Kong. The cover picture shows terbium-doped LaF3 nanoparticles that are surface functionalized by photon-harvesting antenna ligands. Surface capping with antenna ligands leads to ultrabright nanoparticles, with the typical green luminescence signature of the Tb atoms and very long excited-state lifetimes. These lanthanide dots can be incorporated into living cells at nanomolar concentrations for luminescence microscopy imaging. Read the full text of the article at 10.1002/cplu.201600007.

Ultrabright Lanthanide Nanoparticles.

Tb-doped La0.9 Tb0.1 F3 nanoparticles were prepared by a simple and reproducible microwave-assisted synthetic protocol in water. The nanoparticles were characterized by XRD, TEM, dynamic light scattering and inductively coupled plasma atomic emission spectroscopy elemental analysis. Eleven ligands with varying coordination and photosensitizing abilities were designed to bind at the surface of the Tb-doped nanoparticles. The photosensitizing behavior was monitored by electronic absorption spectroscopy and steady-state and time-resolved emission spectroscopy. The two most effective photosensitizing ligands were used to isolate and purify the capped nanoparticles. The composition and spectroscopic properties of these nanoparticles were measured, which revealed either 2660 and 5240 ligands per nanoparticle, molar absorptivities of 7.6×106 and 1.6×107 m-1 cm-1 and luminescence quantum yields of 0.29 and 0.13 in water, respectively. These data correspond to exceptional brightness values of 2.2×106 and 2.1×106 m-1 cm-1 , respectively. The as-prepared nanoparticles were imaged in HeLa cells by fluorescence microscopy, which showed their specific localization in lysosomes.

A smart "off-on" gate for the in situ detection of hydrogen sulphide with Cu(ii)-assisted europium emission.

A water-soluble and emissive Eu-complex (EuL1) bearing a DO3A(Eu3+)-pyridine-aza-crown motif has been prepared and its Cu2+ complex has been demonstrated to be a smart luminescence "off-on" gate for H2S detection in water with a nano-molar detection limit (60 nM). EuL1 binds to Cu2+ ions selectively (KB = 1.2 × 105 M-1) inducing 17-fold luminescence quenching and forming a 1 : 1 stoichiometric complex (EuL1-Cu2+), which responds to H2S selectively with restoration of the original Eu emission of EuL1 followed by a further 40-fold luminescence enhancement, forming a 1 : 1 stoichiometric complex (EuL1-Na2S, KB = 1.5 × 104 M-1). Without Cu2+ ions, EuL1 showed non-specific binding towards H2S with only a 5-fold luminescence enhancement.

Real-time in situ monitoring via europium emission of the photo-release of antitumor cisplatin from a Eu-Pt complex.

A water-soluble light-responsive antitumor agent, PtEuL, based on a cisplatin-linked europium-cyclen complex has been synthesized and evaluated for controlled cisplatin release by linear/two-photon excitation in vitro with concomitant turn-on and long-lived europium emission as a responsive traceable signal.

Photo-reactive charge trapping memory based on lanthanide complex.

Traditional utilization of photo-induced excitons is popularly but restricted in the fields of photovoltaic devices as well as photodetectors, and efforts on broadening its function have always been attempted. However, rare reports are available on organic field effect transistor (OFET) memory employing photo-induced charges. Here, we demonstrate an OFET memory containing a novel organic lanthanide complex Eu(tta)3ppta (Eu(tta)3 = Europium(III) thenoyltrifluoroacetonate, ppta = 2-phenyl-4,6-bis(pyrazol-1-yl)-1,3,5-triazine), in which the photo-induced charges can be successfully trapped and detrapped. The luminescent complex emits intense red emission upon ultraviolet (UV) light excitation and serves as a trapping element of holes injected from the pentacene semiconductor layer. Memory window can be significantly enlarged by light-assisted programming and erasing procedures, during which the photo-induced excitons in the semiconductor layer are separated by voltage bias. The enhancement of memory window is attributed to the increasing number of photo-induced excitons by the UV light. The charges are stored in this luminescent complex for at least 10(4) s after withdrawing voltage bias. The present study on photo-assisted novel memory may motivate the research on a new type of light tunable charge trapping photo-reactive memory devices.

Directional Plk1 inhibition-driven cell cycle interruption using amphiphilic thin-coated peptide-lanthanide upconversion nanomaterials as in vivo tumor suppressors.

Polo-like kinase 1 (Plk1) is a major serine/threonine protein kinase which regulates key mitotic events such as centrosome duplication, spindle assembly and chromosome separation. Overexpression and aberrant activities of Plk1 can be detected in different types of cancer. Given that the unique polo box domain (PBD) pocket provides an excellent drug target for Plk1 binding and inhibition, we have rationally designed multifunctional lanthanide-doped upconversion nanomaterials. NaGdF4:Yb3+, Er3+ (NaGdF4) and BaGdF5:Yb3+, Er3+ (BaGdF5) nanoparticles of two different sizes (60 nm and 10 nm, respectively) have been thin-coated with Plk1 specific peptides (-P1 = PLHSpT, -P2 = PLHSD, and -P3 = GGPLHSpT) to prepare novel nanomaterials. Comparative studies on cellular uptake, anti-cancer activity and imaging properties were then carried out. The experimental data obtained support our original hypothesis that the designed nanomaterials can successfully deliver Plk1 specific peptides into cancer cells causing Plk1 inhibition while simultaneously allowing direct NIR imaging and monitoring. Among the NaGdF4-Pn and BaGdF5-Pn nanoparticle series prepared in this study, NaGdF4-P1 emerged as the best candidate for Plk1 binding and imaging. NaGdF4-P1 can effectively exert cell cycle G2/M arrest and thus selective tumor inhibition both in vitro and in vivo and as such it offers a potentially interesting system for the development of new cancer therapies.