PMID: 11336350May 5, 2001Paper

Differences in the intracellular distribution of acid-sensitive doxorubicin-protein conjugates in comparison to free and liposomal formulated doxorubicin as shown by confocal microscopy

Pharmaceutical Research
U BeyerF Kratz

Abstract

To investigate differences in the cellular uptake and intracellular distribution of protein-bound doxorubicin in comparison to free doxorubicin and a liposomal formulation (CAELYX) METHODS: LXFL 529 lung carcinoma cells were incubated with an acid-sensitive transferrin and albumin conjugate of doxorubicin, a stable albumin doxorubicin conjugate, and free and liposomal doxorubicin for up to 24 h. The uptake of doxorubicin was detected with confocal laser scanning microscopy (CLSM). To investigate the intracellular localization of the anticancer drug, lysosomes, Golgi apparatus, and mitochondria were also stained by various organelle-specific fluorescent markers. In vitro efficacy of the doxorubicin derivatives was examined with the BrdU incorporation assay. The acid-sensitive albumin and transferrin doxorubicin conjugates showed enhanced cytotoxicity in comparison to liposomal doxorubicin, whereas the stable albumin-doxorubicin conjugate showed only marginal activity. Of all compounds tested, doxorubicin showed the highest cytotoxicity. CLSM studies with specific markers for lysosomes, mitochondria, and the Golgi apparatus demonstrated that protein-bound doxorubicin or liberated doxorubicin was accumulated in the mitochondria an...Continue Reading

Citations

Oct 3, 2003·Journal of Molecular Recognition : JMR·Ulrike KraussAnnette G Beck-Sickinger
Apr 13, 2005·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ganna V KalaydaJan Reedijk
Jul 12, 2013·Biomedical Chromatography : BMC·Imran AliMohammed Al Za'abi
Apr 9, 2004·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Bart A J JansenJan Reedijk
Oct 10, 2013·Macromolecular Bioscience·Leto-Aikaterini TzivelekaGeorge Kordas
Nov 24, 2006·American Journal of Physiology. Cell Physiology·Dong Fu, Basil D Roufogalis
Apr 28, 2004·Biomaterials·Valeria PiddubnyakZdzisław Krawczyk
May 25, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Corine C VisserAlbertus G de Boer
Jan 24, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bert J LaoDaniel T Kamei
Dec 19, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Silvio Garattini
Nov 11, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dennis J YoonDaniel T Kamei
Nov 27, 2008·Biochemical and Biophysical Research Communications·Neil Ashley, Joanna Poulton

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