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

• Main Authors: Hsiang-I Tsai (Author), Lijuan Jiang (Author), Xiaowei Zeng (Author), Hongbo Chen (Author), Zihuang Li (Author), Wei Cheng (Author), Jinxie Zhang (Author), Jie Pan (Author), Dong Wan (Author), Li Gao (Author), Zhenhua Xie (Author), Laiqiang Huang (Author), Lin Mei (Author), Gan Liu (Author)
• Format: Book
• Published: Frontiers Media S.A., 2018-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-b-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro 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.

Item Description

1663-9812
10.3389/fphar.2018.00119