Vascular endothelial growth factor-C siRNA delivered via calcium carbonate nanoparticle effectively inhibits lymphangiogenesis and growth of colorectal cancer in vivo.
A nonviral gene carrier, calcium carbonate (CaCO(3))-nanoparticle, was evaluated for the efficient in vitro and in vivo delivery of siRNA-targeting vascular endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO(3)-nanoparticle has a 58-nm diameter and a + 28.6-mV positive surface charge. It is capable of forming a CaCO(3)-nanoparticle-DNA complex and transferring DNA into targeted cells with high transfection efficiency, while effectively protecting the encapsulated DNA from degradation. Further, the CaCO(3)-nanoparticle-DNA complex has no obvious cytotoxicity for LoVo cells, while a liposome-DNA complex exhibited measurable cytotoxicity. LoVo cells transfected with a VEGF-C-targeted small interfering RNA (siRNA) via the CaCO(3)-nanoparticle exhibits significantly reduced VEGF-C expression, as measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, whereas no decrease in VEGF-C expression is observed in cells treated by control transfection. Transfection of LoVo cells with VEGF-C siRNA via the CaCO(3)-nanoparticle also dramatically suppresses tumor lymphangiogenesis, tumor growth, and regional lymph-node metastasis in subcutaneous xenografts. Significant downregulation of VEGF-C messenger RNA expression in a subcutaneous xenograft derived from VEGF-C siRNA-treated LoVo cells was confirmed by real-time PCR, as compared to controls. We conclude that the CaCO(3)-nanoparticle is a novel, nonviral system for the effective delivery of siRNA for cancer gene therapy.
He
Xiao-Wen
XW
Department of General Surgery, Shaoxing First People's Hospital, Shaoxing, China.
Liu
Ting
T
Xiao
Yu
Y
Feng
Ya-Ling
YL
Cheng
Dao-Jin
DJ
Tingting
Guo
G
Zhang
Liyuan
L
Zhang
Yi
Y
Chen
Yu-Xiang
YX
Tingting
Guo
G
Zhang
Liyuan
L
D000818:Animals; D002119:Calcium Carbonate / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D018744:DNA, Plant / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D042583:Lymphangiogenesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection / Q000379:methods; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018744:DNA, Plant; D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D002119:Calcium Carbonate