Selection of optimal sites for TGFB1 gene silencing by chitosan-TPP nanoparticle-mediated delivery of shRNA.
Most human tumors produce high levels of TGF-beta1, whose autocrine and paracrine actions promote tumor cell invasiveness and metastasis. Currently, many experimental therapies that target TGFB1 have utilized antisense DNA or RNA interference (RNAi). Despite the great potential of RNAi, the selection of effective target sites and proper delivery systems for short hairpin RNA (shRNA) remains a significant issue. Here, we used chitosan nanoparticle-mediated delivery of a shRNA-expressing vector to inhibit TGFB1 expression in the human rhabdomyosarcoma cell line RD. Knockdown of TGFB1 by shRNA resulted in a decrease in RD cell growth in vitro and tumorigenicity in nude mice. The efficiency of TGFB1 gene silencing varied with the selection of targeting sites. These data suggest that chitosan nanoparticle-mediated delivery of an shRNA produces efficient TGFB1 knockdown in rhabdomyosarcoma cells and may be a method of choice for shRNA delivery for gene therapy.
Wang
So-Ly
SL
Department of Pathology, Soochow University School of Medicine, Suzhou, China.
Yao
Hui-Hua
HH
Guo
Ling-Ling
LL
Dong
Liang
L
Li
Shi-Gang
SG
Gu
Yong-Ping
YP
Qin
Zheng-Hong
ZH
D000818:Animals; D001483:Base Sequence; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009690:Nucleic Acid Conformation; D011122:Polyphosphates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D011122:Polyphosphates; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D048271:Chitosan; C005692:triphosphoric acid