A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry.

Grafting of δ-aminolevulinic acid (1) moieties on the narrow periphery of a β-cyclodextrin (β-CD) derivative through hydrolysable bonds was implemented, in order to generate a water-soluble, molecular/drug carrier with the capacity to undergo intracellular transformation into protoporphyrin IX (PpIX), an endogenous powerful photosensitizer for photodynamic therapy (PDT). The water-soluble derivative 2 was prepared by esterifying δ-azidolevulinic acid with heptakis(6-hydroxyethylamino-6-deoxy)-β-cyclodextrin, with an average degree of substitution, DS = 3. Delivery of water-soluble, colorless 2 to cells resulted in intense red fluorescence registered by confocal microscopy, evidently due to the engagement of the intracellular machinery towards formation of PpIX.

Protoporphyrin IX-β-cyclodextrin bimodal conjugate: nanosized drug transporter and potent phototoxin.

Topical or systemic administration of 5-aminolevulinic acid (ALA) and its esters results in increased production and accumulation of protoporphyrin IX (PpIX) in cancerous lesions allowing effective application of photodynamic therapy (PDT). The large concentrations of exogenous ALA practically required to bypass the negative feedback control exerted by heme on enzymatic ALA synthesis and the strong dimerization propensity of ALA are shortcomings of the otherwise attractive PpIX biosynthesis. To circumvent these limitations and possibly enhance the phototoxicity of PpIX by adjuvant chemotherapy, covalent bonding of PpIX with a drug carrier, β-cyclodextrin (βCD) was implemented.

Tamoxifen subcellular localization; observation of cell-specific cytotoxicity enhancement by inhibition of mitochondrial ETC complexes I and III.

Recently, a nongenomic cytotoxic component of the chemotherapeutic agent tamoxifen (TAM) has been identified that predominantly triggers mitochondrial events. The present study delineates the intracellular fate of TAM and studies its interaction with a spectrum of cell homeostasis modulators primarily relevant to mitochondria. The subcellular localization of TAM was assessed by confocal fluorescence microscopy.

Per(6-guanidino-6-deoxy)cyclodextrins: synthesis, characterisation and binding behaviour toward selected small molecules and DNA.

Per(6-guanidino-6-deoxy)-cyclodextrins , and are novel derivatives, resulting from homogeneous introduction of the guanidino group at the primary side of alpha-, beta- and gamma-cyclodextrins. The products were obtained from the corresponding amino derivatives, as direct guanidinylation of the known bromo-cyclodextrins provided mixtures. The new compounds were fully characterized by NMR spectroscopy and other analytical methods, and their interaction with guest molecules was studied.