Effects of CXCR4 siRNA/dextran-spermine nanoparticles on CXCR4 expression and serum LDH levels in a mouse model of colorectal cancer metastasis to the liver

Abstract

Liver metastasis is the main cause of mortality related to colorectal cancer. CXCR4 is necessary for the outgrowth of colon cancer micrometastases. In oncology, it has been d emonstrated that several human tumors release lactate dehydrogenase (LDH) into the circulation. CXCR4 gene expression and serum LDH levels are often increased in patients with colorectal cancer. Despite technological advances in cancer therapy, five-year overall survival is still around 50%. Therefore, better treatment needs to be developed. RNA interference (RNAi) is a modern and powerful tool for inhibition of gene expression. However, the rate-limiting step in this technology is effective delivery of RNAi agents. We have investigated a novel strategy of CXCR4 siRNA therapy and its effect on serum LDH levels in a BALB/C mouse model of colorectal cancer metastasis to the liver. Hepatic metastasis was established by injecting a CT26.WT mouse colon carcinoma cell line via the tail vein. Our results demonstrated that CXCR4 siRNA/ dextran-spermine nanoparticles achieved high silencing efficiency with low toxicity. Favorable localization of the nanoparticles was confirmed with CXCR4 gene expression in the liver, that was correlated with serum LDH levels. More research will be needed to determine the effect of CXCR4 silencing on serum LDH levels, which may be a useful marker for predicting liver metastasis in colorectal cancer.

Gene Therapy for Regenerative Medicine

“…Polycation technology based on complex-cell interaction is predicated on the simple and nonspecific electrostatic force, and more enhanced and cell-specific cell transfection are not always expected. The study of enhanced gene delivery based on new technologies of materials is underway [ 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. One of the attractive technologies is based on cell receptor-mediated uptake [ 68 ].…”

“…These cationic polysaccharides were prepared by reductive amination of the oligoamine and periodate-oxidised polysaccharides. Although most of these cationic conjugates formed stable complexes with plasmid DNAs as determined by ethidium-bromide quenching assay [ 56 ], only the dextran-spermine-based polycations were found to be highly effective in transfecting cells in vitro as well as in vivo [ 55 , 56 , 57 , 59 , 60 , 61 , 62 , 63 , 64 ].…”

Potential Applications of Nanomedicine

“…Nanomedicine is new field of science that combines nanomaterials, biomaterials, and biology to generate new class of materials that are able to mimic human cells and tissues. Engineering nanomaterials products specifically biodegradable nanoparticles are great discoveries in the area of nanomedicine technology [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. One strategy for engineering nanoscale materials is to design them in order to culture the cells inside the biomaterials such as natural or synthetic polymers [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”

Small Interfering RNA in Colorectal Cancer Liver Metastasis Therapy

“…18 Small Interfering RNA (siRNA) Technology in CRLM Recently, RNA interference (RNAi) has received considerable attention for its ability to block liver metastasis. 19 RNAi is a biological process that destroys specific messenger RNA (mRNA) molecules and inhibits eukaryotic gene expression. Small interfering RNA (siRNAs) are among the most relevant therapeutic agents.…”