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- Title
Catabolism of Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.
- Authors
Kang, Choong; Kim, Hyunjung; Koo, Hyun-Jung; Park, Jin; An, Gwang; Choi, Joon; Lee, Kyung-Han; Kim, Byung-Tae; Choe, Yearn
- Abstract
Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared Cu-1,4,7,10-tetraazacyclododecane- N, N′, N″, N′″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates.
- Subjects
SERUM; ALBUMINS; BLOOD plasma; LYSOSOMAL storage diseases; XENOGRAFTS
- Publication
Amino Acids, 2016, Vol 48, Issue 7, p1667
- ISSN
0939-4451
- Publication type
Article
- DOI
10.1007/s00726-016-2227-y