Calcium carbonate nanoparticle delivering vascular endothelial growth factor-C siRNA effectively inhibits lymphangiogenesis and growth of gastric cancer in vivo.
A nonviral gene carrier, calcium carbonate (CaCO3) nanoparticle, was evaluated for efficient in vitro and in vivo delivery of small interfering RNA (siRNA) targeting vascular endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO3 nanoparticle has a 58 nm diameter and +28.6 mV positive surface charge. It is capable of forming a CaCO3 nanoparticle-DNA complex and transferring DNA into targeted cells with high transfection efficiency while effectively protecting the encapsulated DNA from degradation. Furthermore, the CaCO3 nanoparticle-DNA complex has no obvious cytotoxicity for SGC-7901 cells, while a liposome-DNA complex exhibited measurable cytotoxicity. SGC-7901 cells transfected with a VEGF-C-targeted siRNA via CaCO3 nanoparticle exhibit significantly reduced VEGF-C expression as measured by real-time PCR and enzyme-linked immunosorbent assay; whereas no decrease in VEGF-C expression is observed in cells treated by control transfection. Transfection of SGC-7901 cells with VEGF-C siRNA via CaCO3 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 SGC-7901 cells was confirmed by real-time PCR as compared to controls. We conclude that CaCO3 nanoparticle is a novel and nonviral system for effective delivery of siRNA for cancer gene therapy.
He
X-w
XW
Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Liu
T
T
Chen
Y-x
YX
Cheng
D-j
DJ
Li
X-r
XR
Xiao
Y
Y
Feng
Y-l
YL
D000818:Animals; D002119:Calcium Carbonate / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; D002119:Calcium Carbonate