Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles.
Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 ± 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy.
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Jeong Yu
JY
Lee
Soo Hyeon
SH
Lee
Mi Hwa
MH
Oh
Jee Seon
JS
Kim
Tae Gwan
TG
Park
Yoon Sung
YS
Nam
D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000737:chemistry; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
D009844:Oligosaccharides; D034741:RNA, Small Interfering; D003840:Deoxycholic Acid; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan