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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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posted on 26.10.2010, 00:00 by 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, Hsian-Rong Tseng
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 (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

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