Micelle-encapsulated IR783 for enhanced photothermal therapy in mouse breast cancer.

Background: Photothermal therapy, an emerging cancer treatment, selectively eliminates lesions using photothermal compounds that convert light into heat. IR783, a near-infrared fluorescent heptamethine cyanine dye, has been used to achieve selective hyperthermic effects in target tissues via near-infrared irradiation. To implement IR783 as a photothermal agent, IR783 biodistribution must be calibrated to achieve a constant and uniform concentration in target cells.

A Stochastic FRET Study on the Core Dimension of Polystyrene--Poly(Polyethylene Glycol Monomethyl Ether Acrylate) Micelles.

Polystyrene--poly(polyethylene glycol monomethyl ether acrylate) (PSt--PPEGA) copolymers featuring pyrene and perylene as the Förster resonance energy transfer (FRET) donor (denoted as D-BCP) and acceptor (denoted as A-BCP), respectively, were synthesized via the reversible addition and fragmentation chain transfer (RAFT) polymerization. These copolymers were then used to form DA-mixed micelles via a dialysis method. The micelles consisted of D-BCP (mole fraction = 0.

RAFT Synthesis and Characterization of Poly(Butyl--2-(,-Dimethylamino)Ethyl Acrylates)--Poly(Polyethylene Glycol Monomethyl Ether Acrylate) as a Photosensitizer Carrier for Photodynamic Therapy.

Polymer micelles are promising drug delivery systems for highly hydrophobic photosensitizers in photodynamic therapy (PDT) applications. We previously developed pH-responsive polymer micelles consisting of poly(styrene--2-(,-dimethylamino)ethyl acrylate)--poly(polyethylene glycol monomethyl ether acrylate) (P(St--DMAEA)--PPEGA) for zinc phthalocyanine (ZnPc) delivery. In this study, poly(butyl--2-(,-dimethylamino)ethyl acrylates)--poly(polyethylene glycol monomethyl ether acrylate) (P(BA--DMAEA)--PPEGA) was synthesized via reversible addition and fragmentation chain transfer (RAFT) polymerization to explore the role of neutral hydrophobic units in photosensitizer delivery.

Effect of tertiary amino groups in the hydrophobic segment of an amphiphilic block copolymer on zinc phthalocyanine encapsulation and photodynamic activity.

Polymer micelles are promising nanocarriers for hydrophobic photosensitizers of photodynamic therapy (PDT). Poly(styrene--(2-(,-dimethylamino)ethyl acrylate))--poly(polyethylene glycol monomethyl ether acrylate) (P(St--DMAEA)--PPEGA; 1) was prepared reversible addition and fragmentation chain transfer (RAFT) polymerization as a carrier for a zinc phthalocyanine (ZnPc) photosensitizer to be used in PDT. The DMAEA-unit composition in the P(St--DMAEA) segment was adjusted to 0.

A fluorescent calix[4]arene with naphthalene units at the upper rim exhibits long fluorescence emission lifetime without fluorescence quenching.

We synthesised a new compound with four naphthyl groups in the upper rims of calix[4]arene (1). Compared to the monomer unit, compound 1 has redshifted absorption and fluorescence, together with high fluorescence quantum yield and long fluorescence lifetime, which is extremely rare because long fluorescence lifetime emission tends to reduce the quantum yield. Single-crystal X-ray analysis and quantum calculations in the S state revealed π-π through-space interactions between naphthalene rings.

FRET Measurement of Polymer Response under Shear.

Polymer solutions under shear flow are often observed in manufacturing processes. Classically, polymer behavior is represented by Kuhn's bead-spring model, in which only the elongation of polymer chains is assumed. In recent years, the compression of polymer chains under shear flow has been reported.

Environment-sensitive emission of anionic hydrogen-bonded urea-derivative-acetate-ion complexes and their aggregation-induced emission enhancement.

Anions often quench fluorescence (FL). However, strong ionic hydrogen bonding between fluorescent dyes and anion molecules has the potential to control the electronic state of FL dyes, creating new functions via non-covalent interactions. Here, we propose an approach, utilising ionic hydrogen bonding between urea groups and anions, to control the electronic states of fluorophores and develop an aggregation-induced emission enhancement (AIEE) system.

Synthesis, photophysical properties, and photodynamic activity of positional isomers of TFPP-glucose conjugates.

The synthesis and characterization of a 'complete set' of positional isomers of tetrakis(perfluorophenyl)porphyrins (TFPP)-glucose conjugates (1OH, 2OH, 3OH, 4OH, and 6OH) are reported herein. The cellular uptake and photocytotoxicity of these conjugates were examined in order to investigate the influence of location of the TFPP moiety on the d-glucose molecule on the biological activity of the conjugates. An In vitro biological evaluation revealed that the certain of these isomers have a greater effect on cellular uptake and cytotoxicity than others.

Syntheses, photophysical properties, and photocytotoxicities of tetrakis(fluorophenyl)porphyrin derivatives bearing 2-hydroxyethylthio groups.

Porphyrin derivatives for photodynamic therapy are frequently modified with hydrophilic groups to improve their water solubility; however, such hydrophilic groups not only improve the solubility but also affect the photodynamic behavior of the compound. The suitable number and pattern of the hydrophilic substituents depend on the nature of the hydrophilic groups. In this article, we explore the optimum architecture for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP) derivatives bearing 2-hydroxyethylthio substituents.

Synthesis, Photophysical Properties, and Biological Evaluation of trans-Bisthioglycosylated Tetrakis(fluorophenyl)chlorin for Photodynamic Therapy.

trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that the trans-bisthioglycosylated structure of 7 enhanced its uptake by HeLa cells and that the chlorin ring of 7 increased the efficiency of reactive oxygen species generation under the standard condition of our photocytotoxicity test. The versatility of 7 in PDT treatment was established using weakly metastatic B16F1 melanoma cells, metastatic 4T1 breast cancer cells, the RGK-1 gastric carcinoma mucosal cell line, and three human glioblastoma cell lines (U87, U251, and T98G).

Sugar and heavy atom effects of glycoconjugated chlorin palladium complex on photocytotoxicity.

Palladium(II) complexes of glycoconjugated porphyrin and pyrrolidine-fused chlorin were prepared to examine sugar and heavy atom effects on in vitro photocytotoxicity. Cellular uptake into HeLa cells was enhanced by introducing sugar units regardless of other features, such as the central ion (free base or palladium(II) ion) and the ring structure (porphyrin or chlorin). The palladium(II) complex of glycoconjugated pyrrolidine-fused chlorin (PdPC2) exerted an excellent degree of photocytotoxicity not only on HeLa cells, but also on metastatic B16-BL6 cells, weakly metastatic B16F1 cells, and metastatic 4T1 cells.

Mitochondrial mode of action of a thymidine-based cisplatin analogue breaks resistance in cancer cells.

Cisplatin analogue complexes with platinum(II) and palladium(II) starting from 3',5'-diamino-3',5'-dideoxy-thymidines were synthesized, both with the D-erythro- and D-threo configurations. Complexes of the general formula [MCl(2)L] were obtained and characterized. NMR spectroscopic measurements and single crystal X-ray structure analysis showed that the metal centers are coordinated to the ligands by the amino groups in 3'- and 5'-positions and not through the thymine moiety.

Plasmon-enhanced luminescence from ultrathin hybrid polymer nanoassemblies for microscopic oxygen sensor application.

Plasmon-enhanced luminescence was developed for luminescent oxygen sensor application. Luminescent polymer Langmuir-Blodgett films containing platinum-porphyrin were assembled plane-to-plane with a silver nanoparticle array. The hybrid polymer nanoassemblies allow more than 10-fold luminescence enhancement in air.

Synthesis, photophysical properties and photocytotoxicity of mono-, di-, tri- and tetra-glucosylated fluorophenylporphyrins.

In order to explore the effect of substitution patterns on the photocytotoxicity of glycoconjugated porphyrins, we synthesized and characterized a 'complete set' of tetrakis(perfluorophenyl)porphyrins having beta-d-glucopyranosylthio groups on the phenyl ring. Among five possible derivatives, trans-substituted S-glucosylated porphyrin trans-2(OH) exerted outstanding photocytotoxicity (EC(50) value was < 5 nM) in HeLa cells. The excellent photocytotoxicity of trans-2(OH) was found to be attributable to several factors, namely high optical transition probability in aqueous media, efficient type I photoreactions and enhanced cellular uptake.

Extended X-ray absorption fine structure study on reaction of anti-tumor platinum complexes with reduced glutathione.

Reactions of cis-diamminedichloroplatinum(II) (cisplatin) and 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) with reduced glutathione, a tripeptide that is abundant in cells, were studied by means of X-ray absorption spectroscopy. Back-scattering amplitudes F(i)(k) and phase shifts Phi(i)(k) were theoretically derived, and validated by applying them to calculate extended X-ray absorption fine structure (EXAFS) oscillations of cisplatin and K(2)[Pt(SCN)(4)] in the solid state. EXAFS oscillations of reaction mixtures of cisplatin or carboplatin with reduced glutathione were fitted to the standard EXAFS equation using the F(i)(k) and Phi(i)(k) functions to give the coordination numbers of N or O atoms (N(N/O)) and of Cl or S atoms (N(Cl/S)).

Antioxidant action of sugar-pendant C60 fullerenes.

The action of C60 fullerene and its derivatives as a radical-scavenging antioxidant has received much attention, but their reactivity toward free radicals and antioxidant capacity have not been well elucidated yet. In the present study, the reactivity of the two types of water-soluble, sugar-pendant C60 fullerenes, C60-1S and C60-2S, toward peroxyl radical and their effect against human plasma lipid peroxidation were measured. The rate constants for the reaction of C60-1S and C60-2S with peroxyl radicals were obtained from their effect on the bleaching of beta-carotene in lipid-SDS micelle system as 4.

Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides.

Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a', 1b', 1a and 1b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a', 2b', 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside.

Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20-Tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient (1)O(2)-generating glycoconjugates.

5,10,15,20-Tetrakis(4-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosylthio)-2,3,5,6-tetrafluorophenyl)porphyrin 2a and its Zn(II), Pd(II), and Pt(II) complexes 2b, 2c, and 2d were prepared in excellent yields by nucleophilic substitution of the corresponding free-base porphyrin and metalloporphyrins with acetyl 2,3,4,6-tetra-O-acetyl-1-thio-beta-d-glucopyranoside. Deprotection of 2a, 2b, 2c, and 2d by alkaline hydrolysis afforded the corresponding S-glucosylated porphyrin 3a and its metal complexes 3b, 3c, and 3d. The structures and purity of all new photosensitizers were confirmed by elemental analysis and (1)H, (13)C, and (19)F NMR, UV-vis, and steady-state luminescence spectroscopy.

In vitro heavy-atom effect of palladium(II) and platinum(II) complexes of pyrrolidine-fused chlorin in photodynamic therapy.

Introduction of a heavy atom into photosensitizers generally facilitates intersystem crossing and improves the quantum yield (Phi(Delta)) of singlet oxygen ((1)O(2)), which is a key species in photodynamic therapy (PDT). However, little information is available about the physiological importance of this heavy-atom effect. The aim of this study is to examine the heavy-atom effect in simple metallochlorins in vitro at the cellular level.

Structure-photodynamic effect relationships of 24 glycoconjugated photosensitizers in HeLa cells.

The photodynamic effect of the glycoconjugated photosensitizer library containing 16 glycoconjugated 5,10,15,20-tetraphenylporphyrins and 8 glycoconjugated 5,10,15,20-tetraphenylchlorins were examined in HeLa cells, and analyzed by two approaches, namely, physiological properties (cellular uptake and reactive oxygen species (ROS)) and structural features of glycoconjugated photosensitizers. All glycoconjugated photosensitizers showed no cytotoxicity in the dark at a concentration of 5 muM. The photocytotoxicity profiles poorly related to the amount of cellular uptake of the photosensitizers.

Syntheses, structural characterization and photophysical properties of 4-(2-pyridyl)-1,2,3-triazole rhenium(I) complexes.

Novel chelators, i.e., 4-(2-pyridyl)-1,2,3-triazole derivatives, were synthesized by means of Cu(I)-catalyzed 1,3-dipolar cycloaddition and used to prepare luminescent Re(I) complexes [ReCl(CO)(3)(Bn-pyta)], [ReCl(CO)(3)(AcGlc-pyta)] and [ReCl(CO)(3)(Glc-pyta)] (Bn-pyta = 1-benzyl-4-(2-pyridyl)-1,2,3-triazole, AcGlc-pyta = 2-(4-(2-pyridyl)-1,2,3-triazol-1-yl)ethyl 2,3,4,6-tetra-O-acetyl-beta-d-glucopyranoside, Glc-pyta = 2-(4-(2-pyridyl)-1,2,3-triazol-1-yl)ethyl beta-d-glucopyranoside).

A general route to pendant C-glycosyl 1,2- and 1,3-diamines.

Practical and convenient preparations of C-glycosyl 1,2- and 1,3-alkanediamines are described. Two 1,2-ethylenediamine derivatives were synthesized from acetylated allyl alpha-C-glycosyl compounds via dibromination, azidation, carbohydrate deprotection, and azide reduction. Four 1,3-propanediamine derivatives were prepared from acetylated sugar halides via C-glycosylation with sodiomalononitrile, followed by the reduction of the nitrile moieties and the deacetylation of the carbohydrate moiety.

Poly[[{μ(3)-tris-[2-(4-phenyl-1,2,3-triazol-1-yl)eth-yl]amine}silver(I)] hexa-fluorido-phosphate].

The title compound, {[Ag(L)]PF(6))(n) {L is tris-[2-(4-phenyl-1,2,3-triazol-1-yl)eth-yl]amine, C(30)H(30)N(10)}, consists of alternating two-dimensional cationic layers of [Ag(L)](+) and anionic PF(6) (-) layers. Each Ag(I) atom is three coordinated in a T-shaped geometry by three N atoms from three ligands. Each ligand links three Ag(I) atoms, generating a two-dimensional network structure with two different metallacycles, A and B.