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:

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.