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; Laiqiang Huang; Lin Mei; Gan Liu

doi:10.3389/fphar.2018.00119

Frontiers in Pharmacology (Feb 2018)

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,
Laiqiang Huang,
Lin Mei,
Gan Liu

Affiliations

Hsiang-I Tsai: School of Life Sciences, Tsinghua University, Beijing, China
Lijuan Jiang: School of Life Sciences, Tsinghua University, Beijing, China
Xiaowei Zeng: School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China
Hongbo Chen: School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China
Zihuang Li: Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen Municipal People's Hospital, Shenzhen, China
Wei Cheng: Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
Jinxie Zhang: School of Life Sciences, Tsinghua University, Beijing, China
Jie Pan: School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin, China
Dong Wan: School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin, China
Li Gao: Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, China
Zhenhua Xie: Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
Laiqiang Huang: School of Life Sciences, Tsinghua University, Beijing, China
Laiqiang Huang: Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
Lin Mei: School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China
Gan Liu: School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, China

DOI: https://doi.org/10.3389/fphar.2018.00119
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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