Dielectrophoresis Nano-separator for Precision Manufacturing of Polymeric
Nanoparticles for Tumor-Targeted Drug Delivery
Sponsored by the Shun Hing Institute of Advanced Engineering
Principal Investigator:
Professor Shih-Chi Chen, Department of Mechanical and Automation Engineering
Co-Investigators:
Prof. Hsiang-fu Kung, Stanley Ho Centre for Emerging Infectious Diseases,
Faculty of Medicine
Prof. Marie Lin, Department of Surgery, Prince of Wales Hospital
Prof. Wen Jung Li, Department of Mechanical and Biological Engineering (City
University of Hong Kong)
Project Team:
-
Dr. Hong Yao, MD/PhD
-
Dr. Shih-Mo Yang, PhD
Introduction
This research aims to
develop a dielectrophoresis (DEP)-based high-throughput nanoparticle separation
technology that enables precise separation of polymeric nanoparticles for
cancer-targeted drug delivery. Using nanoparticles to treat cancer is a
promising therapeutic method. The effectiveness of this technique has been
experimentally proven by numerous research groups on a variety of cancer models
[1]. Studies suggest that precise control of nanoparticles’ sizes and surface
charges may (1) further improve the effectiveness of the treatment and (2)
reduce the related toxicity level. However, due to the solution-based
nanoparticle fabrication procedure, to date there has not been any method
reported in literature to precisely control the sizes and surface charges of
nanoparticles for cancer-targeted treatment; currently, a common size
distribution of polymeric nanoparticle is around 50nm – 2000nm.
In this work, we will
first develop a DEP-based nano-separator that is capable of collecting and
separating nanoparticles according to their specific dimensions, e.g. 100nm ±
10nm, and surface charges. PEI-CyD-FA mediated polymeric nanoparticles, a
promising new cancer-targeting drug developed by our team, will be used in the
DEP device for separation [2, 3]. We will perform in vivo mouse studies with the
separated polymeric nanoparticles in order to investigate and characterize the
level of improvements in terms of cancer-targeting sensitivity and toxicity
control. The developed nanoparticle separation method will be a scalable,
low-cost, and high precision technology that can be widely adopted in
pharmaceutical and medicine manufacturing industry.
Publications
[1] H. Yao, S. Chen, Z. Shen, Y.C. Huang, X. Zhu, X.M. Wang, W. Jiang, Z.F.
Wang, X.W. Bian, E.A. Ling, H.F. Kung, M.C. Lin, “Functional Characterization of
a PEI-CyD-FA-coated Adenovirus as Delivery Vector for Gene Therapy,” Current
Medicinal Chemistry, Vol. 20, No. 20, pp. 2601-08(8), 2013.
[2]
S.M. Yang, H. Yao, D. Zhang, W.J. Li, H.F. Kung, and S. Chen, “Droplet-based
Dielectrophoresis Platform for Polymeric Nanoparticle Separation and Improved
Gene Delivery Efficiency,” Microfluidics and Nanofluidics, Vol. 19,
No. 1, pp. 235-43, 2015.
[3]
S.M. Yang, W. Chen, D. Zhang, and S. Chen, “A Flow-Free Droplet-Based Device for
High Throughput Polymorphic Crystallization,” Lab on a Chip, Vol. 15,
pp. 2680-87, 2015.
References
[1] De Jong, WH and
Borm, PJ, “Drug delivery and nanoparticles: Applications and hazards,” Int. J.
Nanomedicine, 3(2), pp. 133-149, 2008.
[2] Yao, H, Ng, SS,
Tucker, WO, Tsang, YK, Man, K, Wang, XM, Chow, BK, Kung, HF, Tang, GP, and Lin,
MC, “The gene transfection efficiency of a folate-PEI600-cyclodextrin
nanopolymer,” Biomaterials, 30(29), pp.5793-803, 2009.
[3] Yao, H, Ng, SS, Huo,
LF, Chow, KC, Shen, Z, Yang, M, Sze, J, Ko, O, Li, M, Yue, A., Lu, L., Bian, XW,
Kung, HF and Lin, MC, “Effective Melanoma Immunotherapy with Interleukin-2
Delivered by a Novel Polymeric Nanoparticle,” Mol Cancer Ther, 10(6), pp.
1082-92, 2011.