Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer
Abstract Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug na...
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doaj-b6e9d52f75ba47d5b8150e1934cee5102020-12-20T12:27:58ZengNature Publishing GroupScientific Reports2045-23222020-12-0110111410.1038/s41598-020-79125-0Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancerChao Zhang0Fanghua Zhang1Mengnan Han2Xuming Wang3Jie Du4Honglei Zhang5Wei Li6College of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityCollege of Chemistry and Environmental Science, Key Laboratory of Chemical Biology of Hebei Province, Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei UniversityAbstract Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2+ cancer.https://doi.org/10.1038/s41598-020-79125-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chao Zhang Fanghua Zhang Mengnan Han Xuming Wang Jie Du Honglei Zhang Wei Li |
spellingShingle |
Chao Zhang Fanghua Zhang Mengnan Han Xuming Wang Jie Du Honglei Zhang Wei Li Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer Scientific Reports |
author_facet |
Chao Zhang Fanghua Zhang Mengnan Han Xuming Wang Jie Du Honglei Zhang Wei Li |
author_sort |
Chao Zhang |
title |
Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer |
title_short |
Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer |
title_full |
Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer |
title_fullStr |
Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer |
title_full_unstemmed |
Co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-DNA hybrid strands for targeted synergistic chemotherapy of HER2 overexpressing breast cancer |
title_sort |
co-delivery of 5-fluorodeoxyuridine and doxorubicin via gold nanoparticle equipped with affibody-dna hybrid strands for targeted synergistic chemotherapy of her2 overexpressing breast cancer |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-12-01 |
description |
Abstract Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2+ cancer. |
url |
https://doi.org/10.1038/s41598-020-79125-0 |
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