Systemic Administration of Polymer‐Coated Nano‐Graphene to Deliver Drugs to Glioblastoma

Graphene—2D carbon—has received significant attention thanks to its electronic, thermal, and mechanical properties. Recently, nano‐graphene (nGr) has been investigated as a possible platform for biomedical applications. Here, a polymer‐coated nGr to deliver drugs to glioblastoma after systemic administration is reported. A biodegradable, biocompatible poly(lactide) (PLA) coating enables encapsulation and controlled release of the hydrophobic anticancer drug paclitaxel (PTX), and a hydrophilic poly(ethylene glycol) (PEG) shell increases the solubility of the nGr drug delivery system. Importantly, the polymer coating mediates the interaction of nGr with U‐138 glioblastoma cells and decreases cytotoxicity compared with pristine untreated nGr. PLA‐PEG‐coated nGr is also able to encapsulate PTX at 4.15 wt% and sustains prolonged PTX release for at least 19 d. PTX‐loaded nGr‐PLA‐PEGs are shown to kill up to 20% of U‐138 glioblastoma cells in vitro. Furthermore, nGr‐PLA‐PEG and CNT‐PLA‐PEG, two carbon nanomaterials with different shapes, are able to kill U‐138 in vitro as well as free PTX at significantly lower doses of drug. Finally, in vivo biodistribution of nGr‐PLA‐PEG shows accumulation of nGr in intracranial U‐138 glioblastoma xenografts and organs of the reticuloendothelial system.     

Calcium rubies: a family of red-emitting functionalizable indicators suitable for two-photon ca(2+) imaging

We designed Calcium Rubies, a family of functionalizable BAPTA-based red-fluorescent calcium (Ca(2+)) indicators as new tools for biological Ca(2+) imaging. The specificity of this Ca(2+)-indicator family is its side arm, attached on the ethylene glycol bridge that allows coupling the indicator to various groups while leaving open the possibility of aromatic substitutions on the BAPTA core for tuning the Ca(2+)-binding affinity. Using this possibility we now synthesize and characterize three different CaRubies with affinities between 3 and 22 μM. Their long excitation and emission wavelengths (peaks at 586/604 nm) allow their use in otherwise challenging multicolor experiments, e.g., when combining Ca(2+) uncaging or optogenetic stimulation with Ca(2+) imaging in cells expressing fluorescent proteins. We illustrate this capacity by the detection of Ca(2+) transients evoked by blue light in cultured astrocytes expressing CatCh, a light-sensitive Ca(2+)-translocating channelrhodopsin linked to yellow fluorescent protein. Using time-correlated single-photon counting, we measured fluorescence lifetimes for all CaRubies and demonstrate a 10-fold increase in the average lifetime upon Ca(2+) chelation. Since only the fluorescence quantum yield but not the absorbance of the CaRubies is Ca(2+)-dependent, calibrated two-photon fluorescence excitation measurements of absolute Ca(2+) concentrations are feasible.     

Entropic and electrostatic effects on the folding free energy of a surface-attached biomolecule: an experimental and theoretical study

Surface-tethered biomolecules play key roles in many biological processes and biotechnologies. However, while the physical consequences of such surface attachment have seen significant theoretical study, to date this issue has seen relatively little experimental investigation. In response we present here a quantitative experimental and theoretical study of the extent to which attachment to a charged-but otherwise apparently inert-surface alters the folding free energy of a simple biomolecule. Specifically, we have measured the folding free energy of a DNA stem loop both in solution and when site-specifically attached to a negatively charged, hydroxylalkane-coated gold surface. We find that whereas surface attachment is destabilizing at low ionic strength, it becomes stabilizing at ionic strengths above ~130 mM. This behavior presumably reflects two competing mechanisms: excluded volume effects, which stabilize the folded conformation by reducing the entropy of the unfolded state, and electrostatics, which, at lower ionic strengths, destabilizes the more compact folded state via repulsion from the negatively charged surface. To test this hypothesis, we have employed existing theories of the electrostatics of surface-bound polyelectrolytes and the entropy of surface-bound polymers to model both effects. Despite lacking any fitted parameters, these theoretical models quantitatively fit our experimental results, suggesting that, for this system, current knowledge of both surface electrostatics and excluded volume effects is reasonably complete and accurate.     

Adiabatic charge and spin pumping through interacting quantum dots

In this paper we investigate adiabatic charge and spin pumping through interacting quantum dots using non-equilibrium Green's function techniques and the equation-of-motion method. We treat the electronic correlations inside the dot using a Hartree-Fock approximation and succeed in obtaining closed analytic expressions for the Keldysh Green's functions. These allow us to compute charge and spin currents through the quantum dot. Depending on the parameters of the quantum dot and its coupling to the reservoirs, we show that it can be found in two different regimes: the magnetic regime and the non-magnetic regime. In the magnetic regime we find a non-vanishing spin current in addition to the charge current present in both cases.     

Capacity and Covering Numbers

We establish the inequality $1/C_K(E)\ge \int_0^\infty |dK(t)|/N_E(t)$ , where E is a compact metric space, K is a kernel function, C _K is the associated capacity, and N _E (t) denotes the minimal number of sets of diameter t needed to cover E. We give applications to the capacity of generalized Cantor sets, and to the capacity of δ-neighborhoods of a set. We also investigate possible converses to the inequality.     

Nitric oxide release: part II. Therapeutic applications

A wide range of nitric oxide (NO)-releasing materials has emerged as potential therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. In this tutorial review, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing.     

Chemical composition and antibacterial activity of the essential oil of Espeletia nana

The essential oil of the leaves of Espeletia nana Cuatrec., obtained by hydrodistillation, was analyzed by GC-MS, which allowed the identification of 24 components, which made up 99.9% of the oil. The most abundant compounds were a-pinene (38.1%), beta-pinene (17.2%), myrcene (15.0%), spathulenol (4.2%), bicyclogermacrene (4.0%), a-zingiberene (4.0%), and gamma-himachalene (3.7%). Antibacterial activity was tested against Gram-positive and Gram-negative bacteria using the agar disk diffusion method. Activity was observed only against Gram-positive bacteria. MIC values were determined for Staphylococcus aureus ATCC 25923 (200 microg/mL) and Enterococcusfaecalis ATCC 29212 (600 microg/mL).     

Coumarin 314 free radical cation: formation, properties, and reactivity toward phenolic antioxidants

We have explored the photogeneration of the coumarin 314 radical cation by using nanosecond laser excitation at wavelengths longer than 400 nm in benzene, acetonitrile, dichloromethane, and aqueous media. In addition, time-resolved absorption spectroscopy measurements allowed detection of the triplet excited state of coumarin 314 (C(314)) with a maximum absorption at 550 nm in benzene. The triplet excited state has a lifetime of 90 μs in benzene. It is readily quenched by oxygen (k(q) = 5.0 × 10(9) M(-1) s(-1)). From triplet-triplet energy transfer quenching experiments, it is shown that the energy of this triplet excited state is higher than 35 kcal/mol, in accord with the relatively large singlet oxygen quantum yield (Φ(Δ) = 0.25). However, in aqueous media, the coumarin triplet was no longer observed, and instead of that, a long-lived (160 μs in air-equilibrated solutions) free radical cation with a maximum absorbance at 370 nm was detected. The free radical cation generation, which has a quantum yield of 0.2, occurs by electron photoejection. Moreover, density functional theory (DFT) calculations indicate that at least 40% of the electronic density is placed on the nitrogen atom in aqueous media, which explains its lack of reactivity toward oxygen. On the other hand, rate constant values close to the diffusion rate limit in water (>10(9) M(-1) s(-1)) were found for the quenching of the C(314) free radical cation by phenolic antioxidants. The results have been interpreted by an electron-transfer reaction between the phenolic antioxidant and the radical cation where ion pair formation could be involved.     

Strong Traces for Solutions of Multidimensional Scalar Conservation Laws

In this paper we consider multidimensional scalar conservation laws without BV estimates defined in a subset Ω??⁺×? ^d . We show that, with a non-degeneracy hypothesis on the flux, we can define a strong notion of trace at the boundary of Ω reached by L ¹ convergence.