AUTHOR=Tsai Hsiang-I , Jiang Lijuan , Zeng Xiaowei , Chen Hongbo , Li Zihuang , Cheng Wei , Zhang Jinxie , Pan Jie , Wan Dong , Gao Li , Xie Zhenhua , Huang Laiqiang , Mei Lin , Liu Gan 

TITLE=DACHPt-Loaded Nanoparticles Self-assembled from Biodegradable Dendritic Copolymer Polyglutamic Acid-b-D-α-Tocopheryl Polyethylene Glycol 1000 Succinate for Multidrug Resistant Lung Cancer Therapy

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00119

DOI=10.3389/fphar.2018.00119

ISSN=1663-9812

ABSTRACT=<p>The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid-<italic>b</italic>-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-<italic>b</italic>-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile <italic>in vitro</italic> similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.</p>