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A Rapid Pathway Toward a Superb Gene Delivery System: Programming Structural and Functional Diversity into a Supramolecular Nanoparticle Library

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Hao Wang‡§

¶, Kan Liu†, Kuan-Ju Chen‡§

¶, Yujie Lu#, Shutao Wang‡§

¶, Wei-Yu Lin‡§

¶, Feng Guo‡§

, Ken-ichiro Kamei‡§

¶, Yi-Chun Chen‡§

¶, Minori Ohashi‡§

¶, Mingwei Wang‡§

¶, Mitch André Garcia‡§

¶, Xing-Zhong Zhao

, Clifton K.-F. Shen‡§

*, and Hsian-Rong Tseng‡§

¶*

^† College of Electronics and Information Engineering, Wuhan Textile University, Wuhan, 430073, China

^‡ Crump Institute for Molecular Imaging

^§ California NanoSystems Institute

Department of Molecular and Medical Pharmacology

^¶ Institute for Molecular Medicine

University of California, Los Angeles, California 90095, United States

^# Center for Molecular Imaging, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Pressler Street SRB 330A, Houston, Texas 77030, United States

Department of Physics, School of Physics, Center of Nanoscience and Nanotechnology, Wuhan University, Wuhan, 430072, China

ACS Nano, 2010, 4 (10), pp 6235–6243

DOI: 10.1021/nn101908e

Publication Date (Web): October 6, 2010

* Address correspondence to kshen@mednet.ucla.edu, hrtseng@mednet.ucla.edu.,

These authors contributed equally to the work

Section:

Biochemical Methods

Abstract

Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNASNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNASNPs library identified the DNASNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNASNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.