{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang M"],"funding":["Science and Technology Commission of Shanghai Municipality","National Natural Science Foundation of China"],"pagination":["E162"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6160908"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(3)"],"pubmed_abstract":["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."],"journal":["Pharmaceutics"],"pubmed_title":["Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy."],"pmcid":["PMC6160908"],"funding_grant_id":["81761148028 and 21773026","15520711400 and 17540712000"],"pubmed_authors":["Zheng Y","Zhu J","Majoral JP","Wang S","Zhang M","Guo R","Mignani S","Caminade AM","Shi X"],"additional_accession":[]},"is_claimable":false,"name":"Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy.","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.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Sep","modification":"2025-04-21T18:17:43.555Z","creation":"2019-03-26T23:58:29Z"},"accession":"S-EPMC6160908","cross_references":{"pubmed":["30235881"],"doi":["10.3390/pharmaceutics10030162"]}}