Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy
We present here the development of multifunctional doxorubicin (DOX)-conjugated poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release and targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the periphery of partially acetylated and...
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| Format: | Article |
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MDPI AG
2018-09-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/10/3/162 |
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| author | Mengen Zhang Jingyi Zhu Yun Zheng Rui Guo Shige Wang Serge Mignani Anne-Marie Caminade Jean-Pierre Majoral Xiangyang Shi |
| author_facet | Mengen Zhang Jingyi Zhu Yun Zheng Rui Guo Shige Wang Serge Mignani Anne-Marie Caminade Jean-Pierre Majoral Xiangyang Shi |
| author_sort | Mengen Zhang |
| collection | DOAJ |
| description | We present here the development of multifunctional doxorubicin (DOX)-conjugated poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release and targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the periphery of partially acetylated and folic acid (FA)-modified generation 5 (G5) PAMAM dendrimers through a pH-sensitive cis-aconityl linkage to form the G5.NHAc-FA-DOX conjugates. The formed dendrimer conjugates were well characterized using different methods. We show that DOX release from the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher release rate under an acidic pH condition (pH = 5 or 6, close to the acidic pH of tumor microenvironment) than under a physiological pH condition. Both in vitro cytotoxicity evaluation and cell morphological observation demonstrate that the therapeutic activity of dendrimer-DOX conjugates against cancer cells is absolutely related to the DOX drug released. More importantly, the FA conjugation onto the dendrimers allowed a specific targeting to cancer cells overexpressing FA receptors (FAR), and allowed targeted inhibition of cancer cells. The developed G5.NHAc-FA-DOX conjugates may be used as a promising nanodevice for targeted cancer chemotherapy. |
| first_indexed | 2024-04-11T11:51:53Z |
| format | Article |
| id | doaj.art-4543f2feff6d4a45adaf751a790f0fd4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T11:51:53Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4543f2feff6d4a45adaf751a790f0fd42022-12-22T04:25:18ZengMDPI AGPharmaceutics1999-49232018-09-0110316210.3390/pharmaceutics10030162pharmaceutics10030162Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer TherapyMengen Zhang0Jingyi Zhu1Yun Zheng2Rui Guo3Shige Wang4Serge Mignani5Anne-Marie Caminade6Jean-Pierre Majoral7Xiangyang Shi8Key Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaCollege of Materials Science and Engineering, Donghua University, Shanghai 201620, ChinaKey Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaKey Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaKey Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaCentro de Química da Madeira (CQM), Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, PortugalLaboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse CEDEX 4, FranceLaboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, BP 44099, 31077 Toulouse CEDEX 4, FranceKey Laboratory of Science & Technology of Eco-Textile, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, ChinaWe present here the development of multifunctional doxorubicin (DOX)-conjugated poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release and targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the periphery of partially acetylated and folic acid (FA)-modified generation 5 (G5) PAMAM dendrimers through a pH-sensitive cis-aconityl linkage to form the G5.NHAc-FA-DOX conjugates. The formed dendrimer conjugates were well characterized using different methods. We show that DOX release from the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher release rate under an acidic pH condition (pH = 5 or 6, close to the acidic pH of tumor microenvironment) than under a physiological pH condition. Both in vitro cytotoxicity evaluation and cell morphological observation demonstrate that the therapeutic activity of dendrimer-DOX conjugates against cancer cells is absolutely related to the DOX drug released. More importantly, the FA conjugation onto the dendrimers allowed a specific targeting to cancer cells overexpressing FA receptors (FAR), and allowed targeted inhibition of cancer cells. The developed G5.NHAc-FA-DOX conjugates may be used as a promising nanodevice for targeted cancer chemotherapy.http://www.mdpi.com/1999-4923/10/3/162PAMAM dendrimerdoxorubicincis-aconityl linkagepH-responsive releasetargeted cancer therapy |
| spellingShingle | Mengen Zhang Jingyi Zhu Yun Zheng Rui Guo Shige Wang Serge Mignani Anne-Marie Caminade Jean-Pierre Majoral Xiangyang Shi Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy Pharmaceutics PAMAM dendrimer doxorubicin cis-aconityl linkage pH-responsive release targeted cancer therapy |
| title | Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy |
| title_full | Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy |
| title_fullStr | Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy |
| title_full_unstemmed | Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy |
| title_short | Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy |
| title_sort | doxorubicin conjugated pamam dendrimers for ph responsive drug release and folic acid targeted cancer therapy |
| topic | PAMAM dendrimer doxorubicin cis-aconityl linkage pH-responsive release targeted cancer therapy |
| url | http://www.mdpi.com/1999-4923/10/3/162 |
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