366-13-2Relevant articles and documents
Screening and optimization of ligand conjugates for lysosomal targeting
Meerovich, Igor,Koshkaryev, Alexander,Thekkedath, Ritesh,Torchilin, Vladimir P.
, p. 2271 - 2282 (2011)
The use of lysosome-targeted liposomes may significantly improve the delivery of therapeutic enzymes and chaperones into lysosomes for the treatment of lysosomal storage disorders. The aim of this research was to synthesize new potentially lysosomotropic ligands on a base of Neutral Red and rhodamine B and to study their ability to enhance specific lysosomal delivery of surface-modified liposomes loaded with a model compound, fluorescein isothiocyanate-dextran (FD). The delivery of these liposomes and their content to lysosomes in HeLa cells was investigated by confocal immunofluorescent microscopy, subcellular fractionation, and flow cytometry. Confocal microscopy demonstrated that liposomes modified with derivatives of rhodamine B provide a good rate of colocalization with the specific lysosomal markers. The comparison of fluorescence of FD in lysosomes isolated by subcellular fractionation also showed that the efficiency of lysosomal delivery of the liposomal load by liposomes modified with some of synthesized ligands was significantly higher compared to that with plain liposomes. These results were additionally confirmed by flow cytometry of the intact cells treated with liposomes loaded with 5-dodecanoylaminofluorescein di-β-d-galactopyranoside, a specific substrate for the intralysosomal β-galactosidase, using a number of cell lines, including macrophages with induced phenotype of lysosomal enzyme deficiency; two of the synthesized ligands-rhodamine B DSPE-PEG2k-amide and 6-(3-(DSPE-PEG2k)-thioureido) rhodamine B-demonstrated enhanced lysosomal delivery, in some cases, higher than that for commercially available rhodamine B octadecyl ester, with the best results (the enhancement of the lysosomal delivery up to 75% greater in comparison to plain liposomes) shown for the cells with induced lysosomal enzyme deficiency phenotype. Use of liposomes modified with rhodamine B derivatives may be advantageous for the development of drug delivery systems for the treatment of lysosome-associated disorders.
Studies on the radiolytically produced transients of neutral red: Triplet and reduced radicals
Sing,Pal,Sapre
, p. 44 - 52 (2007/10/03)
The spectral and kinetic properties of reduced radicals and the triplet state of neutral red (NR), a phenazine-based dye, have been investigated using pulse radiolysis technique. A mixed water-isopropanol-acetone solvent has been used to study the reduced radicals of NR for a wide pH range of about 1-13, due to limitation of solubility of the dye in aqueous solutions particularly above pH 8. From pH-dependent absorption studies it has been established that the reduced radicals of NR can exist in four different prototropic forms in solution. Three pKa values for the corresponding prototropic equilibria have been estimated. The formation and decay rate constants of reduced radicals have also been measured. The triplet state characteristics of the dye have been investigated in neat benzene solutions, both in the presence and in the absence of triplet sensitizers. The T1 → Tn absorption spectrum and decay kinetics of the triplet state have been measured. The triplet state energy (ET) of NR in benzene have been estimated to be within 36-42 kcal mol-1, using an energy transfer method.
