Anti-tumor effects of anti-VEGF siRNA encapsulated with PLGA microspheres in mice.
The suppression of gene expression of vascular endothelial growth factor (VEGF) which regulates tumor angiogenesis in vivo and is an important factor in tumor growth represents a novel approach to cancer treatment. Although small interfering RNA (siRNA) has rapidly become a major tool in gene therapy and is a key inhibitory factor of gene expression, its effect is temporary. The present study investigates the preparation of long-term sustained release poly (dl-lactic/glycolic acid) (PLGA) microspheres encapsulating anti-VEGF siRNA with a carrier (arginine or branched polyethylenimine) using the w/o/w in-water drying method and their anti-tumor activities. The ratio (%) of encapsulated siRNA increased when arginine or PEI was added to the inner water phase during preparation. The release of siRNA from microspheres in phosphate buffer (pH 7.4) was sustained for over one month. The anti-tumor effects of microspheres in vivo were evaluated in mice bearing S-180 tumors. An intra-tumor injection of microspheres with encapsulated siRNA obviously suppressed tumor growth. These results indicate that the microspheres of anti-VEGF siRNA with a transfection agent (carrier) have achieved a higher and sustained suppressive effect on VEGF gene expression and should be a practically useful preparation.
Murata
Naoyuki
N
Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi Hachioji Tokyo 192-0392, Japan.
Takashima
Yuuki
Y
Toyoshima
Kosei
K
Yamamoto
Mari
M
Okada
Hiroaki
H
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005260:Female; D020868:Gene Silencing; D015552:Injections, Intralesional; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D008863:Microspheres; D009368:Neoplasm Transplantation; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
D004337:Drug Carriers; D011108:Polymers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid