Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer
The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytot...
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| Format: | Article |
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MDPI AG
2018-09-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/10/9/311 |
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| author | Hang-Kang Chen Shu-Mei Zhang Junn-Liang Chang Hsin-Chien Chen Yi-Chun Lin Cheng-Ping Shih Huey-Kang Sytwu Mei-Cho Fang Yuan-Yung Lin Chao-Yin Kuo Ai-Ho Liao Yueng-Hsiang Chu Chih-Hung Wang |
| author_facet | Hang-Kang Chen Shu-Mei Zhang Junn-Liang Chang Hsin-Chien Chen Yi-Chun Lin Cheng-Ping Shih Huey-Kang Sytwu Mei-Cho Fang Yuan-Yung Lin Chao-Yin Kuo Ai-Ho Liao Yueng-Hsiang Chu Chih-Hung Wang |
| author_sort | Hang-Kang Chen |
| collection | DOAJ |
| description | The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP to interact with human serum albumin and then sonicated the resulting CDDP‒albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into severe combined immunodeficiency mice and used IVIS® bioluminescence imaging to determine the tumor xenograft formation and size. Twice weekly (until Day 33), we administered CDDP only, CDDP + MBs + US, CDDP-MBs, or CDDP-MBs + US intravenously by tail-vein injection. The US treatment was administered at the tumor site immediately after injection. The in vivo systemic distribution of CDDP indicated that the kidney was the most vulnerable organ, followed by the liver, and then the inner ear. However, CDDP uptake into the kidney and liver was significantly decreased in both the CDDP-MBs and CDDP-MBs + US groups, suggesting that MB binding significantly reduced the systemic toxicity of CDDP. The CDDP-MBs + US treatment reduced the tumor size as effectively as conventional CDDP-only chemotherapy. Therefore, the combination of CDDP-MBs with ultrasound is effective and significantly attenuates CDDP-associated nephrotoxicity, indicating a promising clinical potential for this approach. |
| first_indexed | 2024-03-12T10:05:09Z |
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| id | doaj.art-358ada5302d944e5a839616ae5d59dcf |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T10:05:09Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-358ada5302d944e5a839616ae5d59dcf2023-09-02T11:18:52ZengMDPI AGCancers2072-66942018-09-0110931110.3390/cancers10090311cancers10090311Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck CancerHang-Kang Chen0Shu-Mei Zhang1Junn-Liang Chang2Hsin-Chien Chen3Yi-Chun Lin4Cheng-Ping Shih5Huey-Kang Sytwu6Mei-Cho Fang7Yuan-Yung Lin8Chao-Yin Kuo9Ai-Ho Liao10Yueng-Hsiang Chu11Chih-Hung Wang12Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, TaiwanDepartment of Pathology, Taoyuan Armed Forces General Hospital, Taoyuan 32551, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, TaiwanLaboratory Animal Center, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanThe use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP to interact with human serum albumin and then sonicated the resulting CDDP‒albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into severe combined immunodeficiency mice and used IVIS® bioluminescence imaging to determine the tumor xenograft formation and size. Twice weekly (until Day 33), we administered CDDP only, CDDP + MBs + US, CDDP-MBs, or CDDP-MBs + US intravenously by tail-vein injection. The US treatment was administered at the tumor site immediately after injection. The in vivo systemic distribution of CDDP indicated that the kidney was the most vulnerable organ, followed by the liver, and then the inner ear. However, CDDP uptake into the kidney and liver was significantly decreased in both the CDDP-MBs and CDDP-MBs + US groups, suggesting that MB binding significantly reduced the systemic toxicity of CDDP. The CDDP-MBs + US treatment reduced the tumor size as effectively as conventional CDDP-only chemotherapy. Therefore, the combination of CDDP-MBs with ultrasound is effective and significantly attenuates CDDP-associated nephrotoxicity, indicating a promising clinical potential for this approach.http://www.mdpi.com/2072-6694/10/9/311ultrasoundmicrobubblecisplatinnephrotoxicityhead and neck cancerchemotherapy |
| spellingShingle | Hang-Kang Chen Shu-Mei Zhang Junn-Liang Chang Hsin-Chien Chen Yi-Chun Lin Cheng-Ping Shih Huey-Kang Sytwu Mei-Cho Fang Yuan-Yung Lin Chao-Yin Kuo Ai-Ho Liao Yueng-Hsiang Chu Chih-Hung Wang Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer Cancers ultrasound microbubble cisplatin nephrotoxicity head and neck cancer chemotherapy |
| title | Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer |
| title_full | Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer |
| title_fullStr | Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer |
| title_full_unstemmed | Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer |
| title_short | Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer |
| title_sort | insonation of systemically delivered cisplatin loaded microbubbles significantly attenuates nephrotoxicity of chemotherapy in experimental models of head and neck cancer |
| topic | ultrasound microbubble cisplatin nephrotoxicity head and neck cancer chemotherapy |
| url | http://www.mdpi.com/2072-6694/10/9/311 |
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