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

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

doi:10.3389/fphar.2018.00119

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

Front Pharmacol. 2018 Feb 21:9:119. doi: 10.3389/fphar.2018.00119. eCollection 2018.

Authors

Hsiang-I Tsai¹, Lijuan Jiang¹, Xiaowei Zeng², Hongbo Chen², Zihuang Li³, Wei Cheng⁴, Jinxie Zhang¹, Jie Pan⁵, Dong Wan⁵, Li Gao⁶, Zhenhua Xie⁴, Laiqiang Huang^{1

4}, Lin Mei², Gan Liu²

Affiliations

¹ School of Life Sciences, Tsinghua University, Beijing, China.
² School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China.
³ Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen Municipal People's Hospital, Shenzhen, China.
⁴ Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
⁵ School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin, China.
⁶ Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, China.

Abstract

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.

Keywords: DACHPt; TPGS; dendritic copolymers; multidrug resistance; nanoparticles.