Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes
Abstract Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) lig...
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| Veröffentlicht in: | Biomaterials 2015-07, Vol.57, p.1-11 |
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| creator | Li, Qingpo Tang, Qin Zhang, Peizun Wang, Zuhua Zhao, Tiantian Zhou, Jialin Li, Hongrui Ding, Qian Li, Wei Hu, Fuqiang Du, Yongzhong Yuan, Hong Chen, Shuqing Gao, Jianqing Zhan, Jinbiao You, Jian |
| description | Abstract Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer. |
| doi_str_mv | 10.1016/j.biomaterials.2015.04.009 |
| format | Article |
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In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.04.009</identifier><identifier>PMID: 25956192</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Animals ; Antibiotics, Antineoplastic - chemistry ; Antibiotics, Antineoplastic - therapeutic use ; Antibody-mediated targeted delivery ; Biocompatibility ; Biomedical materials ; Cell Line, Tumor ; Delayed-Action Preparations - chemistry ; Dentistry ; Doxorubicin - administration & dosage ; Doxorubicin - analogs & derivatives ; Doxorubicin - chemistry ; Drug Delivery Systems ; Effectiveness ; Female ; HER2 antibody ; Hollow gold nanospheres ; Humans ; Hyperthermia, Induced ; Immunoconjugates - chemistry ; Immunoconjugates - therapeutic use ; Light ; Light-sensitive liposomes ; Liposomes ; Mice ; Mice, Nude ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Ovary - drug effects ; Ovary - metabolism ; Ovary - pathology ; Phototherapy ; Photothermal-chemotherapy ; Polyethylene Glycols - administration & dosage ; Polyethylene Glycols - chemistry ; Receptor, ErbB-2 - antagonists & inhibitors ; Receptor, ErbB-2 - metabolism ; Surgical implants ; Toxicity ; Tumors</subject><ispartof>Biomaterials, 2015-07, Vol.57, p.1-11</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-30121d9f0a685fe25c17b4b213fa0e307ecff69fcd3bd54a96c542a3af4fcb243</citedby><cites>FETCH-LOGICAL-c431t-30121d9f0a685fe25c17b4b213fa0e307ecff69fcd3bd54a96c542a3af4fcb243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2015.04.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25956192$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Qingpo</creatorcontrib><creatorcontrib>Tang, Qin</creatorcontrib><creatorcontrib>Zhang, Peizun</creatorcontrib><creatorcontrib>Wang, Zuhua</creatorcontrib><creatorcontrib>Zhao, Tiantian</creatorcontrib><creatorcontrib>Zhou, Jialin</creatorcontrib><creatorcontrib>Li, Hongrui</creatorcontrib><creatorcontrib>Ding, Qian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Hu, Fuqiang</creatorcontrib><creatorcontrib>Du, Yongzhong</creatorcontrib><creatorcontrib>Yuan, Hong</creatorcontrib><creatorcontrib>Chen, Shuqing</creatorcontrib><creatorcontrib>Gao, Jianqing</creatorcontrib><creatorcontrib>Zhan, Jinbiao</creatorcontrib><creatorcontrib>You, Jian</creatorcontrib><title>Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer.</description><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - chemistry</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Antibody-mediated targeted delivery</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Cell Line, Tumor</subject><subject>Delayed-Action Preparations - chemistry</subject><subject>Dentistry</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - analogs & derivatives</subject><subject>Doxorubicin - chemistry</subject><subject>Drug Delivery Systems</subject><subject>Effectiveness</subject><subject>Female</subject><subject>HER2 antibody</subject><subject>Hollow gold nanospheres</subject><subject>Humans</subject><subject>Hyperthermia, Induced</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunoconjugates - therapeutic use</subject><subject>Light</subject><subject>Light-sensitive liposomes</subject><subject>Liposomes</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovary - drug effects</subject><subject>Ovary - metabolism</subject><subject>Ovary - pathology</subject><subject>Phototherapy</subject><subject>Photothermal-chemotherapy</subject><subject>Polyethylene Glycols - administration & dosage</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Receptor, ErbB-2 - antagonists & inhibitors</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Surgical implants</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAQxy0EokvhFVDEiUvC-CvZcEBC5aNIlTgAZ8uxx10vSRzspLAP0nufhSfDYQtCnHqyPf79ZzTzH0KeUago0PrFvup8GPSM0es-VQyorEBUAO09sqHbZlvKFuR9sgEqWNnWlJ2QRyntIb9BsIfkhMlW1rRlG3J9vgx6LHDyFuOg--Iyhu_zrnDazCEWEQ1O-VKyQo-z74L1mAocd3o0WMw7_HmTJjTeeePnQ2bsb86s37HIOfzVGg-u6P3lbi4TjsnnIBY2_Ahx6bJuLHvdYY82M1NIYcD0mDxwuTV8cnueki_v3n4-Oy8vPr7_cPb6ojSC07nkQBm1rQNdb6VDJg1tOtExyp0G5NCgca5unbG8s1LotjZSMM21E850TPBT8vyYd4rh24JpVoNPBvtejxiWpGjTAKcgob4DytmW0W0NGX15RE0MKUV0aop-0PGgKKjVQbVX_zqoVgcVCJUdzOKnt3WWbkD7V_rHsgy8OQKYB3PlMapkPOZ5W5_dmpUN_m51Xv2XxvR-zM71X_GAaR-WOK4aqhJToD6tu7SuEpUAXNYN_wXv_s2r</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Li, Qingpo</creator><creator>Tang, Qin</creator><creator>Zhang, Peizun</creator><creator>Wang, Zuhua</creator><creator>Zhao, Tiantian</creator><creator>Zhou, Jialin</creator><creator>Li, Hongrui</creator><creator>Ding, Qian</creator><creator>Li, Wei</creator><creator>Hu, Fuqiang</creator><creator>Du, Yongzhong</creator><creator>Yuan, Hong</creator><creator>Chen, Shuqing</creator><creator>Gao, Jianqing</creator><creator>Zhan, Jinbiao</creator><creator>You, Jian</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20150701</creationdate><title>Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes</title><author>Li, Qingpo ; Tang, Qin ; Zhang, Peizun ; Wang, Zuhua ; Zhao, Tiantian ; Zhou, Jialin ; Li, Hongrui ; Ding, Qian ; Li, Wei ; Hu, Fuqiang ; Du, Yongzhong ; Yuan, Hong ; Chen, Shuqing ; Gao, Jianqing ; Zhan, Jinbiao ; You, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-30121d9f0a685fe25c17b4b213fa0e307ecff69fcd3bd54a96c542a3af4fcb243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - chemistry</topic><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Antibody-mediated targeted delivery</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Cell Line, Tumor</topic><topic>Delayed-Action Preparations - chemistry</topic><topic>Dentistry</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - analogs & derivatives</topic><topic>Doxorubicin - chemistry</topic><topic>Drug Delivery Systems</topic><topic>Effectiveness</topic><topic>Female</topic><topic>HER2 antibody</topic><topic>Hollow gold nanospheres</topic><topic>Humans</topic><topic>Hyperthermia, Induced</topic><topic>Immunoconjugates - chemistry</topic><topic>Immunoconjugates - therapeutic use</topic><topic>Light</topic><topic>Light-sensitive liposomes</topic><topic>Liposomes</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovary - drug effects</topic><topic>Ovary - metabolism</topic><topic>Ovary - pathology</topic><topic>Phototherapy</topic><topic>Photothermal-chemotherapy</topic><topic>Polyethylene Glycols - administration & dosage</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Receptor, ErbB-2 - antagonists & inhibitors</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Surgical implants</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Qingpo</creatorcontrib><creatorcontrib>Tang, Qin</creatorcontrib><creatorcontrib>Zhang, Peizun</creatorcontrib><creatorcontrib>Wang, Zuhua</creatorcontrib><creatorcontrib>Zhao, Tiantian</creatorcontrib><creatorcontrib>Zhou, Jialin</creatorcontrib><creatorcontrib>Li, Hongrui</creatorcontrib><creatorcontrib>Ding, Qian</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Hu, Fuqiang</creatorcontrib><creatorcontrib>Du, Yongzhong</creatorcontrib><creatorcontrib>Yuan, Hong</creatorcontrib><creatorcontrib>Chen, Shuqing</creatorcontrib><creatorcontrib>Gao, Jianqing</creatorcontrib><creatorcontrib>Zhan, Jinbiao</creatorcontrib><creatorcontrib>You, Jian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Qingpo</au><au>Tang, Qin</au><au>Zhang, Peizun</au><au>Wang, Zuhua</au><au>Zhao, Tiantian</au><au>Zhou, Jialin</au><au>Li, Hongrui</au><au>Ding, Qian</au><au>Li, Wei</au><au>Hu, Fuqiang</au><au>Du, Yongzhong</au><au>Yuan, Hong</au><au>Chen, Shuqing</au><au>Gao, Jianqing</au><au>Zhan, Jinbiao</au><au>You, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>57</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>25956192</pmid><doi>10.1016/j.biomaterials.2015.04.009</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Biomaterials, 2015-07, Vol.57, p.1-11 |
| issn | 0142-9612 1878-5905 |
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| subjects | Advanced Basic Science Animals Antibiotics, Antineoplastic - chemistry Antibiotics, Antineoplastic - therapeutic use Antibody-mediated targeted delivery Biocompatibility Biomedical materials Cell Line, Tumor Delayed-Action Preparations - chemistry Dentistry Doxorubicin - administration & dosage Doxorubicin - analogs & derivatives Doxorubicin - chemistry Drug Delivery Systems Effectiveness Female HER2 antibody Hollow gold nanospheres Humans Hyperthermia, Induced Immunoconjugates - chemistry Immunoconjugates - therapeutic use Light Light-sensitive liposomes Liposomes Mice Mice, Nude Ovarian Neoplasms - drug therapy Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Ovary - drug effects Ovary - metabolism Ovary - pathology Phototherapy Photothermal-chemotherapy Polyethylene Glycols - administration & dosage Polyethylene Glycols - chemistry Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Surgical implants Toxicity Tumors |
| title | Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes |
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