Evaluation of antitumor activity of survivin short interfering RNA delivered by lipid nanoparticles in colon cancer in vitro and in vivo

Abstract

Survivin has been overexpressed in numerous types of cancer and is associated with a poor clinical outcome. A number of various approaches have been used to counteract survivin in order to inhibit tumor growth or promote cell apoptosis. The present study aimed to evaluate the efficiency and antitumor effect of a survivin-targeted short interfering RNA (siRNA) delivery system using lipid nanoparticles for the treatment of colon cancer. Survivin siRNA (si-survivin) nanoliposomes were prepared and transfected into LoVo cells. The mRNA expression level of survivin was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Cell viability was evaluated by MTT assay. LoVo-bearing nude mice were treated with si-survivin intratumorally or intravenously. Tumor growth in LoVo-bearing mice was monitored and recorded, and tumor samples were obtained for evaluation of survivin expression levels using RT-qPCR, western blotting and immunohischemical staining. The expression level of survivin was significantly reduced by nanoliposomal si-survivin along with cell proliferation inhibition in vitro. Intravenous administration of si-survivin nanoliposomes may significantly inhibit tumor growth with less toxicity compared with doxorubicin hydrochloride treatment in LoVo-bearing mice. Nanoliposomal si-survivin may significantly reduce the expression level of survivin and inhibit cell proliferation of colon cancer cells in vitro and in vivo. si-survivin delivered by lipid nanoparticles may be a potential treatment approach for colon cancer.

Hairpin–Hairpin Molecular Beacon Interactions for Detection of Survivin mRNA in Malignant SW480 Cells

“…29−35 Recently, AlShamaileh et al 36 have succeeded in applying an aptamer-mediated survivin RNAi to alleviate the multidrug resistance and 5-fluorouracil to kill colorectal cancer stem cells. The antitumor effects of Sur siRNA delivered with lipid nanocarriers to colon cancer cells have also been reported by Wang et al 37 Recent progress in cancer therapy targeting survivin protein and silencing its gene BIRC5 by neutralizing the messenger RNA has been reviewed by Mazur et al 38 Liposomal nanoparticles have been utilized for drug delivery in cancer therapy owing to their biocompatibility and wide range of options for easy tunability to adjust to the given requirements, including targeted delivery of 3-bromopyruvate to suppress aerobic glycolysis and adenosine 5′-triphosphate production, 39 delivery of chemotherapeutic drugs, 40,41 and cancer cell detection. 42,43 The oligonucleotide molecular beacons (MBs), introduced by Tyagi and Kramer 3 have been widely applied as a biosensing platform to recognize single-stranded DNA.…”

“…The problems encountered in this respect have been analyzed by us ,, and others. − Recently, AlShamaileh et al have succeeded in applying an aptamer-mediated survivin RNAi to alleviate the multidrug resistance and 5-fluorouracil to kill colorectal cancer stem cells. The antitumor effects of Sur siRNA delivered with lipid nanocarriers to colon cancer cells have also been reported by Wang et al Recent progress in cancer therapy targeting survivin protein and silencing its gene BIRC5 by neutralizing the messenger RNA has been reviewed by Mazur et al…”

Lipid-Based Drug Delivery Nanoplatforms for Colorectal Cancer Therapy

“…These advantages make liposomes particularly useful in cancer therapy. Today, liposomal DDSs are being extensively studied in various capacities, such as in the application of conventional chemical drugs [ 46 , 47 ], biomolecules [ 48 , 49 ], gene deliveries [ 50 , 51 ], and immune therapies [ 48 , 52 ].…”

“…A number of techniques have been developed to increase the stability and selectivity of the lipoplex by changing the surface charge of the outer layer and adding cell-specific targeting functions. For example, T. Wang et al constructed cationic-LCLs by combining distearoyl-phosphatidylcholine (DSPC), cholesterol, dioctadecyl-dimethylammonium chloride (DODAC), and N-palmitoyl-sphingosine-1-succinyl (PEG-CerC16) at a 25/45/25/2.5 molar ratio [ 50 ]. The constructed nanoliposomes effectively encapsulate the survivin siRNA: DODAC bound to the survivin siRNA to form a lipoplex, and the PEG-modified lipid outer layer increased the residence time in circulation.…”

“…The constructed nanoliposomes effectively encapsulate the survivin siRNA: DODAC bound to the survivin siRNA to form a lipoplex, and the PEG-modified lipid outer layer increased the residence time in circulation. The siRNA/cationic-LCLs significantly reduced the expression level of survivin and inhibited the cell proliferation of CRC cells both in vitro and in vivo [ 50 ]. This study verified that lipid nanoparticles could be a potent vector for delivering nuclear acids to treat colon cancer.…”