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Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models

Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors. A pharmacokinetics study found that CDDP can bind to human serum albumin (HSA), which is the most abundant plasma protein in serum. HSA has the advantage of being a nanocarrier and c...

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Autores principales: Park, Cho Rong, Kim, Hyo Young, Song, Myung Geun, Lee, Yun-Sang, Youn, Hyewon, Chung, June-Key, Cheon, Gi Jeong, Kang, Keon Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663476/
https://www.ncbi.nlm.nih.gov/pubmed/33114661
http://dx.doi.org/10.3390/ijms21217932
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author Park, Cho Rong
Kim, Hyo Young
Song, Myung Geun
Lee, Yun-Sang
Youn, Hyewon
Chung, June-Key
Cheon, Gi Jeong
Kang, Keon Wook
author_facet Park, Cho Rong
Kim, Hyo Young
Song, Myung Geun
Lee, Yun-Sang
Youn, Hyewon
Chung, June-Key
Cheon, Gi Jeong
Kang, Keon Wook
author_sort Park, Cho Rong
collection PubMed
description Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors. A pharmacokinetics study found that CDDP can bind to human serum albumin (HSA), which is the most abundant plasma protein in serum. HSA has the advantage of being a nanocarrier and can accumulate in tumors by passive targeting and active targeting mediated by the secreted protein acidic and rich in cysteine (SPARC). In this study, we investigated the possibility of using a CDDP–HSA complex (HSA–CDDP) as a SPARC-mediated therapeutic agent. To investigate the HSA-dependent therapeutic effect of HSA–CDDP, we used two types of U87MG glioma cells that express SPARC differently. HSA–CDDP was highly taken up in SPARC expressing cells and this uptake was enhanced with exogenous SPARC treatment in cells with low expression of SPARC. The cytotoxicity of HSA–CDDP was also higher in SPARC-expressing cells. In the tumor model, HSA–CDDP showed a similar tumor growth and survival rate to CDDP only in SPARC-expressing tumor models. The biosafety test indicated that HSA–CDDP was less nephrotoxic than CDDP, based on blood markers and histopathology examination. Our findings show that HSA–CDDP has the potential to be a novel therapeutic agent for SPARC-expressing tumors, enhancing the tumor targeting effect by HSA and reducing the nephrotoxicity of CDDP.
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spelling pubmed-76634762020-11-14 Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models Park, Cho Rong Kim, Hyo Young Song, Myung Geun Lee, Yun-Sang Youn, Hyewon Chung, June-Key Cheon, Gi Jeong Kang, Keon Wook Int J Mol Sci Article Cisplatin (cis-diamminedichloroplatinum (II), CDDP) is a chemotherapeutic drug widely used against many solid tumors. A pharmacokinetics study found that CDDP can bind to human serum albumin (HSA), which is the most abundant plasma protein in serum. HSA has the advantage of being a nanocarrier and can accumulate in tumors by passive targeting and active targeting mediated by the secreted protein acidic and rich in cysteine (SPARC). In this study, we investigated the possibility of using a CDDP–HSA complex (HSA–CDDP) as a SPARC-mediated therapeutic agent. To investigate the HSA-dependent therapeutic effect of HSA–CDDP, we used two types of U87MG glioma cells that express SPARC differently. HSA–CDDP was highly taken up in SPARC expressing cells and this uptake was enhanced with exogenous SPARC treatment in cells with low expression of SPARC. The cytotoxicity of HSA–CDDP was also higher in SPARC-expressing cells. In the tumor model, HSA–CDDP showed a similar tumor growth and survival rate to CDDP only in SPARC-expressing tumor models. The biosafety test indicated that HSA–CDDP was less nephrotoxic than CDDP, based on blood markers and histopathology examination. Our findings show that HSA–CDDP has the potential to be a novel therapeutic agent for SPARC-expressing tumors, enhancing the tumor targeting effect by HSA and reducing the nephrotoxicity of CDDP. MDPI 2020-10-26 /pmc/articles/PMC7663476/ /pubmed/33114661 http://dx.doi.org/10.3390/ijms21217932 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Cho Rong
Kim, Hyo Young
Song, Myung Geun
Lee, Yun-Sang
Youn, Hyewon
Chung, June-Key
Cheon, Gi Jeong
Kang, Keon Wook
Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title_full Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title_fullStr Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title_full_unstemmed Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title_short Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models
title_sort efficacy and safety of human serum albumin–cisplatin complex in u87mg xenograft mouse models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663476/
https://www.ncbi.nlm.nih.gov/pubmed/33114661
http://dx.doi.org/10.3390/ijms21217932
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