%0 Journal Article
%T Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy
%A Anne-Marie Caminade
%A Jean-Pierre Majoral
%A Jingyi Zhu
%A Mengen Zhang
%A Rui Guo
%A Serge Mignani
%A Shige Wang
%A Xiangyang Shi
%A Yun Zheng
%J Archive of "Pharmaceutics".
%D 2018
%R 10.3390/pharmaceutics10030162
%X 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
%K PAMAM dendrimer
%K doxorubicin
%K cis-aconityl linkage
%K pH-responsive release
%K targeted cancer therapy
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160908/