Cationized dextran nanoparticle-encapsulated CXCR4-siRNA enhanced correlation between CXCR4 expression and serum alkaline phosphatase in a mouse model of colorectal cancer.
OBJECTIVE
The failure of colorectal cancer treatments is partly due to overexpression of CXCR4 by tumor cells, which plays a critical role in cell metastasis. Moreover, serum alkaline phosphatase (ALP) levels are frequently elevated in patients with metastatic colorectal cancer. A polysaccharide, dextran, was chosen as the vector of siRNA. Spermine was conjugated to oxidized dextran by reductive amination process to obtain cationized dextran, so-called dextran-spermine, in order to prepare CXCR4-siRNAs/dextran-spermine nanoparticles. The fabricated nanoparticles were used in order to investigate whether downregulation of CXCR4 expression could affect serum ALP in mouse models of colorectal cancer.


METHODS
Colorectal cancer was established in BALB/C mice following injection of mouse colon carcinoma cells CT.26WT through the tail vein. CXCR4 siRNA for two sites of the target gene was administered following injection of naked siRNA or siRNA encapsulated into nanoparticles.


RESULTS
In vivo animal data revealed that CXCR4 silencing by dextran-spermine nanoparticles significantly downregulated CXCR4 expression compared with naked CXCR4 siRNA. Furthermore, there was correlation between CXCR4 expression and serum ALP.


CONCLUSIONS
CXCR4 siRNA/dextran-spermine nanoparticles appear to be highly effective, and may be suitable for further in vivo applications. Further research evaluation will be needed to determine the effect of CXCR4 silencing on serum ALP levels, which may be a useful marker to predict liver metastasis in colorectal cancer.
Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
Fatemeh
F
Abedini
Hossein
H
Hosseinkhani
Maznah
M
Ismail
Abraham J
AJ
Domb
Abdul Rahman
AR
Omar
Pei Pei
PP
Chong
Po-Da
PD
Hong
Dah-Shyong
DS
Yu
Ira-Yudovin
IY
Farber
D000469:Alkaline Phosphatase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002412:Cations / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003911:Dextrans / Q000737:chemistry*; D015536:Down-Regulation; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D013096:Spermine / Q000737:chemistry
C514936:CXCR4 protein, mouse; D002412:Cations; D003911:Dextrans; D053769:Nanocapsules; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D013096:Spermine; D000469:Alkaline Phosphatase