Regulation of redox balance using a biocompatible nanoplatform enhances phototherapy efficacy and suppresses tumor metastasis

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment.

Amplified oxidative stress achieved by modulating redox homeostasis with PDA–MB for highly effective synergistic phototherapy to inhibit primary tumors and metastases.     

Spectroscopy and reactivity of a photogenerated tryptophan radical in a structurally defined protein environment

Near-UV irradiation of structurally characterized [Re(I)(CO)3(1,10-phenanthroline)(Q107H)](W48F/Y72F/H83Q/Y108W)AzM(II) [Az = Pseudomonas aeruginosa azurin, M = Cu, Zn]/[Co(NH3)5Cl]Cl2 produces a tryptophan radical (W108*) with unprecedented kinetic stability. After rapid formation (k = 2.8 x 106 s-1), the radical persists for more than 5 h at room temperature in the folded ReAzM(II) structure. The absorption spectrum of ReAz(W108*)M(II) exhibits maxima at 512 and 536 nm. Oxidation of K4[Mo(CN)8] by ReAz(W108*)Zn(II) places the W108*/W108 reduction potential in the protein above 0.8 V vs NHE.     

Immobilization of single-stranded deoxyribonucleic acid on gold electrode with self-assembled aminoethanethiol monolayer for DNA electrochemical sensor applications

A synthesized 24-mer single-stranded deoxyribonucleic acid (ssDNA) was covalently immobilized onto a self-assembled aminoethanethiol monolayer modified gold electrode, using water-soluble 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (EDC). The covalently immobilized ssDNAs were hybridized with complementary ssDNA (cDNA) or yAL(3) gene in solution, forming double-stranded DNAs (dsDNA). Meanwhile, daunomycin as an electrochemical active intercalator in the hybridization buffer solution was intercalated into the dsDNA to form a dsDNA/daunomycin system on the gold electrode surface, which was used for DNA electrochemical sensor. The cathodic waves of daunomycin bound to the double-stranded DNA (dsDNA) by linear sweep voltammetry were utilized to detect the cDNA. The cathodic peak current (i(pc)) of duanomycin was linearly related to the concentrations of cDNA between 0.1 mug ml(-1) and 0.1 ng ml(-1). The detection limit was about 30 pg ml(-1).     

Ultrathin self-assembled polymeric films on solid surfaces. I. Synthesis and characterization of acrylate copolymers containing alkyl disulfide side chains

Copolymers of 2-hydroxyethyl acrylate and 2-methoxyethyl acrylate with variable compositions were synthesized, fractionated, and characterized by ¹H-NMR, IR, GPC, and viscometry. These copolymers were further modified via polymer analog esterification of copolymer hydroxy groups by a series of disulfide-containing carboxylic acids including lipoic acid and (n-pentyldithio) alkyl carboxylic acids (n-C₅H₁₁SS(CH₂)m? COOH, m = 10, 15, 22) in the presence of 1,3-dicyclohexylcarbodiimide (DCC). Esterification reactions were quantitative for copolymers possessing hydroxy monomer contents ≤ 40% when excess acid and DCC were present for sufficiently long reaction times (2–4 days) at room temperature. Copolymer DSC analysis demonstrates a systematic variation of T_g with copolymer composition in good agreement with ideal mixing theory. These disulfide-bearing copolymers spontaneously yield two-dimensional ultrathin polymer films with side chain-dependent layer thicknesses of 20–45 Å by solution adsorption onto freshly deposited gold surfaces. Such ultrathin polymer films are expected to have diverse applications as bound polymeric surface modification reagents. © 1993 John Wiley & Sons, Inc.     

Isoindole Cycloadditions. Part III: The Synthesis of "Windscreen Wiper" and Other N-Bridged Cavity Systems

The thermal addition of N-carbobenzyloxyisoindole (N-Z isoindole) 11a, generated by the reaction of 3,6-di(2-pyridyl)-s-tetrazine 9 with N-Z 7-azabenzonorbornadiene 8a, onto dimethyl tricyclo[4.2.1.0^2.5]nona-3,7-diene-3,4-dicarboxylate 17 occurred site selectively at the cyclobutene -bond to form a stereoisomeric mixture of 1 : 1-adducts 18 and 19, in which the bent-frame isomer 19 was dominant (ratio 5 : 1). In contrast, N-benzyl tetrafluoroisoindole 11c reacted with 17 only under high-pressure conditions (14 kbar, RT, 4 days) to afford 1 : 1-adducts at the cyclobutene site, in which the extended-frame isomer 18c was dominant and the accompanying bent-frame product 19c reverted to starting materials soon after isolation. These same stereoselectivities were used to prepare "windscreen wiper" compound 28c having two mobile N-benzyl substituents attached to a rigid scaffold by the reaction of N-benzyl tetrafluoroisoindole 11c with tetramethyl tetracyclo[4.4.1.0.^2,5.0^7.10]undeca-3,8-diene-3,4,7,8-tetracarboxylate 23. Cavity bis-(cyclobutene-1,2-diester) 6 reacted with N-benzyl tetrafluoroisoindole 11c twice over to produce cavity structure 36 with two O- and two N-benzyl bridges on the inner face, whereas the narrower cavity bis-alkene 32 stopped at the 1 : 1-addition stage. The dynamics of the Z-group in the dual adducts 26a–28a are discussed briefly and key adducts and cavity systems have been structurally evaluated by X-ray crystallography, VT NMR, and molecular modeling.     

Electron tunneling through molecular media: a density functional study of Au/Dithiol/Au systems.

We report a density functional theory study of the electronic properties of n-alkanedithiols (CnS2, with n=4, 8 and 12) sandwiched between two Au(111) infinite slab electrodes. We investigate the influence of the distance between the two electrodes and of the molecular chain length, tilt angle, and coverage on the local density of states (LDOS) at the Fermi energy (E(f)). We find that the (small) value of the LDOS at Ef near the center of the molecular wires--a quantity that is related to the tunneling current--is mainly determined by the length n of the alkane chains: it originates from the tails of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) which are broadened by the interaction with the electrodes, and decays exponentially with the length of the molecular wire. This opens a nonresonance tunneling channel for charge transport at small bias voltages. While the length of the hydrocarbon chain appears to be the determining factor, the tilt angle of the molecular wires with respect to the electrode surfaces, and therefore the distance between these, has a small influence on the LDOS at the center of the molecule, while the effect of coverage can be ignored. The picture which emerges from these calculations is totally consistent with a through-bond tunneling mechanism.     

MEASUREMENTS OF CHAIN INTERPENETRATION OF POLYMER GLASSES

The concept of entanglement provides the basis of our current understanding of the flow behavior of polymer melts, Current techniques developed to investigate the degree of interpenetration of polymer chains only provide indirectly the information of the degree of entanglement in a relatively large scale （several to tens of nanometer）. In this article, we report ^1H-NMR spectroscopy with dipolar filters under fast magic angle spinning for probing chain interpenetration of polymer glasses at the molecular level.     

青霉素G钾盐在CTAB胶束中的水解及其抑制

以紫外光谱法研究了青霉素G钾盐(Pen-K)在十六烷基三甲基溴化铵（CTAB）胶束体系中的水解反应, 并探讨了水解反应机理.结果表明, CTAB胶束对Pen-K的水解具有抑制作用; Pen-K在CTAB胶束体系水解时,体系pH值的变化与在水中相似, 表明H＋浓度对这种抑制作用影响较小.红外光谱和微极性研究表明,部分Pen-K钾盐定位于CTAB胶束栅栏层中, 增加了其稳定性.     

Comparison between ab Initio and Modified INDO-MO Calculations of N20

Both STO-3G ab initio and s-p separation-type-modified INDO semiempirical methods were applied to molecular-orbital calculation of the N₂₀ molecule. From these two methods, the optimized bond distances between the nearest N atoms (d_n-n) and the most calculated thermodynamic data are close to each other. The positive values of ΔH_a° and ΔG_a° for the atomization reaction in this work prove that N₂₀ is stable. In contrast to conventional INDO and MINDO/3, but similar to former AMI and MNDO calculations, both ΔH_r° and ΔG_r° are positive in the formation reaction, which indicates that N₂₀ belongs to the category of high-energy molecules.     

Chemically modified resins for solid-phase extraction

The packings most widely used for solid-phase extraction are hydrophobic and make poor surface contact with aqueous samples unless the resins are first treated with an activating organic solvent such as methanol. Insertion of an acetyl- or hydroxymethyl group into a porous polystyrene-divinylbenzene resin provides a more hydrophilic surface that is easily wetted by water alone. Small columns of the chemically modified resins were found to be very efficient for the solid-phase extraction of many types of organic solutes from aqueous samples. Comparative recovery studies showed that the modified resins are superior to both silica packings and unmodified organic resins for the solid-phase extraction of organic compounds, and especially for polar organics such as phenols.