Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

Photodynamic Therapy

New polymer synthesis by nitroxide mediated living radical polymerizations.

Dendrimers in biomedical applications--reflections on the field.

Polyoxometalates (POMs) are discrete anionic metaloxygen clusters which can be regarded as soluble oxide fragments. They exhibit a great diversity of sizes, nuclearities, and shapes. They are built from the connection of {MOx} polyhedra, M being a d-block element in high oxidation state, usually VIV,V, MoVI, or WVI.1 While these species have been known for almost two centuries, they still attract much interest partly based on their large domains of applications. They play a great role in various areas ranging from catalysis,2 medicine,3 electrochemistry,4 photochromism,5 to magnetism.6 This palette of applications is intrinsically due to the combination of their added value properties (redox properties, large sizes, high negative charges, nucleophilicity...). Parallel to this domain, the organic-inorganic hybrids area has followed a similar expansion during the last 10 years. The concept of organic-inorganic hybrid materials * To whom correspondence should be addressed. E-mail: dolbecq@ chimie.uvsq.fr. Chem. Rev. 2010, 110, 6009–6048 6009

Hybrid Organic−Inorganic Polyoxometalate Compounds: From Structural Diversity to Applications

Polycaprolactone (PCL) is an important polymer due to its mechanical properties, miscibility with a large range of other polymers and biodegradability. Two main pathways to produce polycaprolactone have been described in the literature: the polycondensation of a hydroxycarboxylic acid: 6-hydroxyhexanoic acid, and the ring-opening polymerisation (ROP) of a lactone: e-caprolactone (e-CL). This critical review summarises the different conditions which have been described to synthesise PCL, and gives a broad overview of the different catalytic systems that were used (enzymatic, organic and metal catalyst systems). A surprising variety of catalytic systems have been studied, touching on virtually every section of the periodic table. A detailed list of reaction conditions and catalysts/initiators is given and reaction mechanisms are presented where known. Emphasis is put on the ROP pathway due to its prevalence in the literature and the superior polymer that is obtained. In addition, ineffective systems that have been tried to catalyse the production of PCL are included in the electronic supplementary information for completeness (141 references).

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Synthesis of polycaprolactone: a review

Photodynamic therapy (PDT) is emerging as a new strategy for the conservative treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg-O-alpha-GalOH)(3), TPP(p-Deg-O-beta-GalOH)(3), TPP(p-Deg-O-alpha-ManOH)(3), and their S-analogues were synthesized to obtain efficient photosensitizers with some retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization, and photoactivity have been examined in human retinoblastoma cells (Y79). After preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O-beta-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) was 40-45% inhibited, indicating a possible cell-sugar-receptor saturation. High photoactivity was observed for the two alpha-galacto/manno porphyrins 8 and 10 (LD(50) = 0.05 and 0.35 muM, respectively) at 514 nm and low fluence (1 J/cm(2)). Analysis by MALDI-TOF mass spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates and a good stability of the S-glycoside porphyrins. On the basis of these in vitro data, TPP(p-Deg-O-alpha-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) were selected for in vivo studies.

Photodynamic Efficiency of Diethylene Glycol-Linked Glycoconjugated Porphyrins in Human Retinoblastoma Cells

Dendrimer Design: How to Circumvent the Dilemma of a Reduction of Steps or an Increase of Function Multiplicity?

Neutral phosphorus-containing dendrimers with aldehyde groups at the periphery have been analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) up to generation four. Although the expected quasi-molecular ion is generally observed, the mass spectral pattern, presence of fragments and adducts related to the original skeleton, is highly relevant to the sample preparation (nature of the matrix: 2-5-dihydroxybenzoic acid (2.5-DHB), 1,8-dihydroxy-9[10H]-anthracenone (dithranol), 6-azathiothymine, 2,4,6-trihydroxyacetophenon, 7-hydroxycoumarin or 2-anthramine, and addition of alkali metal salts). The dithranol matrix with addition of LiI offers milder conditions; however, abundant fragments are still observed for the higher generation dendrimers. Investigation of these effects in connection with SEC, NMR, and MALDI-TOFMS studies of UV preirradiated dendrimers allows the assumption to be made that fragmentation occurs in MALDI due to the relatively strong absorption of the dendrimers at 337 nm. Fragmentations and formation of adducts involve nitrogen-nitrogen bond cleavage, imine metathesis, and reaction of aldehyde groups with internal imino groups.

MALDI TOF mass spectrometry for the characterization of phosphorus-containing dendrimers. Scope and limitations

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of polystyrenes prepared by 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)-mediated living free radical polymerization has been performed using two different matrices. A complete assignment of the observed peaks could be proposed, owing to the experimental resolution which allowed us to display the isotopic distribution. With the 1,8-dihydroxy-9(10H)-anthracenone (dithranol)/silver trifluoroacetate system, a major part of the charged chains undergoes gas phase fragmentation during the analysis. This phenomenon, only minor for conventionnally prepared polystyrene, is particularly enhanced when the chains contain a TEMPO-based alkoxyamine end group. In contrast, the dead chains with no alkoxyamine end group are properly detected. When using the 2,5-dihydroxybenzoic acid (DHB) matrix without added salt, only protonation occurs involving the alkoxyamine functionality. Only the TEMPO-capped polystyrene chains are observed an...

MALDI-TOF Mass Spectrometry Analysis of TEMPO-Capped Polystyrene

Extraction of biotinylated peptides by streptavidin magnetic beads has been directly coupled to the MALDI-TOF mass analysis. The elution of peptides from the beads is achieved by first mixing the beads with the MALDI matrix solution and removing, after a few minutes, the beads with a magnet; then, the matrix solution containing the biotinylated peptide is directly mass analyzed by MALDI. Three examples are presented to show the capabilities of this procedure to detect biotinylated peptides present at very low concentrations in complex mixtures. Detection limits of less than 100 fmol can be achieved. Such a coupling strategy is of great interest to investigate peptide/protein interactions.

Jean-Claude Blais

Papers

Photodynamic Efficiency of Diethylene Glycol-Linked Glycoconjugated Porphyrins in Human Retinoblastoma Cells

Dendrimer Design: How to Circumvent the Dilemma of a Reduction of Steps or an Increase of Function Multiplicity?

MALDI TOF mass spectrometry for the characterization of phosphorus-containing dendrimers. Scope and limitations

MALDI-TOF Mass Spectrometry Analysis of TEMPO-Capped Polystyrene

Coupling of MALDI-TOF Mass Analysis to the Separation of Biotinylated Peptides by Magnetic Streptavidin Beads