Research Article
The Synergistic Anticancer Effect of Dual
Drug- (Cisplatin/Epigallocatechin Gallate) Loaded Gelatin
Nanoparticles for Lung Cancer Treatment
Yin-Ju Chen,
1,2,3
Zhi-Weng Wang,
4
Tung-Ling Lu,
1
Clinton B. Gomez,
5
Hsu-Wei Fang,
4,6
Yang Wei ,
4
and Ching-Li Tseng
1,3,7,8
1
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University,
Taipei City 110, Taiwan
2
Department of Radiation Oncology, Taipei Medical University Hospital, Taipei City 110, Taiwan
3
International Ph. D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University,
Taipei City 110, Taiwan
4
Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei City 110, Taiwan
5
Department of Industrial Pharmacy, College of Pharmacy, University of the Philippines Manila, Manila,
1000 Metro Manila, Philippines
6
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town,
Miaoli County 35053, Taiwan
7
Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan
8
International Ph. D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University,
Taipei City 110, Taiwan
Correspondence should be addressed to Yang Wei; wei38@mail.ntut.edu.tw and Ching-Li Tseng; chingli@tmu.edu.tw
Received 2 April 2020; Revised 16 June 2020; Accepted 29 June 2020; Published 5 August 2020
Academic Editor: Ana Espinosa
Copyright © 2020 Yin-Ju Chen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer
treatment. Unfortunately, cisplatin resistance is a common cause of therapeutic failure. The ability to overcome chemoresistance is
crucial to the effective treatment of lung cancer. Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea,
has been shown to suppress the rapid proliferation of cancer cells, including lung cancer. We tested whether nanoparticles (NPs)
carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer
cells. Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual
drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP). The particle size and zeta potential were
examined by dynamic light scattering (DLS). The morphological structure of GE-Pt NPs was observed by transmission electron
microscopy (TEM). In vitro testing was performed using a human lung adenocarcinoma cell line (A549). A cytotoxicity
examination was performed, using a WST-8 cell proliferation assay. Intracellular cisplatin content was quantified by inductively
coupled plasma mass spectrometry (ICP-MS). In conclusion, we successfully prepared GE-Pt NPs, as spherical structures,
approximately 75 nm in diameter, with a positive charge (+19:83 ± 0:25 mV). The encapsulation rate of cisplatin in GE-Pt
was about 63.7%, and the EGCG loading rate was around 89%. A relatively low concentration of GE-Pt NPs (EGCG
5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone. The GE-Pt NPs are freely taken up
by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level. We consider that combination
therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be
used in the treatment of lung cancer.
Hindawi
Journal of Nanomaterials
Volume 2020, Article ID 9181549, 15 pages
https://doi.org/10.1155/2020/9181549