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Dual-functionalized calcium nanocomplexes for transfection of cancerous and stem cells: Low molecular weight polycation-mediated colloidal stability and ATP-mediated endosomal release

  • Choi, Yeon Su (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Kim, Kyoungnam (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Ryu, Kitae (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Cho, Hana (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Cho, Yong-Yeon (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Lee, Joo Young (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Lee, Hye Suk (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Kim, Byung Gon (Department of Brain Science and Department of Neurology, School of Medicine, Ajou University) ;
  • Song, Soo Chang (Center for Biomaterials, Korea Institute of Science and Technology (KIST)) ;
  • Kang, Han Chang (Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea)
  • Received : 2018.02.17
  • Accepted : 2018.03.19
  • Published : 2018.08.25

Abstract

To overcome colloidal instability of calcium phosphate nanoparticles in gene delivery, colloidally stable and endosomolytic $Ca^{2+}-based$ pDNA nanocomplexes (NCs) were designed by a surface coating of biocompatible polycations (PCs; low molecular weight branched polyethyleneimine [bPEI], protamine sulfate and ${\varepsilon}-polylysine$) and the addition of natural and endosomolytic ATP, respectively. Without remarkable cytotoxicity and colloidal instability, $Ca^{2+}/ATP-pDNA/bPEI_{1.8kDa}$ NCs having $[bPEI_{1.8kDa}]=3.6{\mu}g$ showed 5.8-fold and 4.4-fold higher transfection efficiencies than $bPEI_{25kDa}/pDNA$ NCs in HepG2 cells and dental pulp stem cells, respectively. In conclusion, pH-sensitive endosomolytic ATP and $Ca^{2+}-based$ gene complexes could be potentials as effective and safe gene delivery vectors in various cells.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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