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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2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Cho Rong Park Hyo Young Kim Myung Geun Song Yun-Sang Lee Hyewon Youn June-Key Chung Gi Jeong Cheon Keon Wook Kang |
| author_facet | Cho Rong Park Hyo Young Kim Myung Geun Song Yun-Sang Lee Hyewon Youn June-Key Chung Gi Jeong Cheon Keon Wook Kang |
| author_sort | Cho Rong Park |
| collection | DOAJ |
| 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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| language | English |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-107ec291eb624f0491157ce8c088797f2023-11-20T18:34:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121793210.3390/ijms21217932Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse ModelsCho Rong Park0Hyo Young Kim1Myung Geun Song2Yun-Sang Lee3Hyewon Youn4June-Key Chung5Gi Jeong Cheon6Keon Wook Kang7Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaDepartment of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, KoreaCisplatin (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.https://www.mdpi.com/1422-0067/21/21/7932cisplatin (CDDP)human serum albumin (HSA)cancer therapeuticsdrug delivery |
| spellingShingle | Cho Rong Park Hyo Young Kim Myung Geun Song Yun-Sang Lee Hyewon Youn June-Key Chung Gi Jeong Cheon Keon Wook Kang Efficacy and Safety of Human Serum Albumin–Cisplatin Complex in U87MG Xenograft Mouse Models International Journal of Molecular Sciences cisplatin (CDDP) human serum albumin (HSA) cancer therapeutics drug delivery |
| 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 | cisplatin (CDDP) human serum albumin (HSA) cancer therapeutics drug delivery |
| url | https://www.mdpi.com/1422-0067/21/21/7932 |
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