Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery.
The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression.
Yeon Lim
YL
Jang
Sook Hee
SH
Ku
So
S
Jin
Jae Hyung
JH
Park
Won Jong
WJ
Kim
Ick Chan
IC
Kwon
Sun Hwa
SH
Kim
Ji Hoon
JH
Jeong
D001692:Biological Transport; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D004355:Drug Stability; D020868:Gene Silencing; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D004337:Drug Carriers; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D006820:Hyaluronic Acid