title: Glutamine-chitosan modified calcium phosphate nanoparticles for efficient siRNA delivery and osteogenic differentiation.
abstract: RNA interference (RNAi)-based therapy using small interfering RNA (siRNA) exhibits great potential to treat diseases. Although calcium phosphate (CaP)-based systems are attractive options to deliver nucleic acids due to their good biocompatibility and high affinity with nucleic acids, they are limited by uncontrollable particle formation and inconsistent transfection efficiencies. In this study, we developed a stable CaP nanocarrier system with enhanced intracellular uptake by adding highly cationic, glutamine-conjugated oligochitosan (Gln-OChi). CaP nanoparticles coated with Gln-OChi (CaP/Gln-OChi) significantly enhanced gene transfection and knockdown efficiency in both immortalized cell line (HeLa) and primary mesenchymal stem cells (MSCs) with minimal cytotoxicity. The osteogenic bioactivity of siRNA-loaded CaP/Gln-OChi particles was further confirmed in three-dimensional environments by using photocrosslinkable chitosan hydrogels encapsulating MSCs and particles loaded with siRNA targeting noggin, a bone morphogenetic protein antagonist. These findings suggest that our CaP/Gln-OChi nanocarrier provides an efficient and safe gene delivery system for therapeutic applications.
authors.affiliation: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
authors.forename: Bogyu
authors.initials: B
authors.lastname: Choi
authors.affiliation: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Cui
authors.affiliation: Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, Los Angeles, California 90095, USA.
authors.forename: Soyon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA ; Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, Los Angeles, California 90095, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wu
authors.affiliation: Division of Advanced Prosthodontics, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, California 90095, USA ; Department of Bioengineering, University of California Los Angeles, 410 Westwood Plaza, Los Angeles, California 90095, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Lee