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Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA.

Cui D, Zhang C, Liu B, Shu Y, Du T, Shu D, Wang K, Dai F, Liu Y, Li C, Pan F, Yang Y, Ni J, Li H, Brand-Saberi B, Guo P - Sci Rep (2015)

Bottom Line: Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models.Apoptosis of gastric cancer cells was observed.All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

ABSTRACT
Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

No MeSH data available.


Related in: MedlinePlus

The BRCAA1 silencing effects of FA-pRNA-3WJ-BRCAA1siRNA assayed by (a) qRT-PCR (GADPH is the endogenous control)(there existed statistical difference between FA-pRNA-3WJ-BRCAA1siRNA group and FA-pRNA-3WJ-Scramb-siRNA group, P < 0.01) and (b) western blot assay (β-actin bands served as loading control).
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f3: The BRCAA1 silencing effects of FA-pRNA-3WJ-BRCAA1siRNA assayed by (a) qRT-PCR (GADPH is the endogenous control)(there existed statistical difference between FA-pRNA-3WJ-BRCAA1siRNA group and FA-pRNA-3WJ-Scramb-siRNA group, P < 0.01) and (b) western blot assay (β-actin bands served as loading control).

Mentions: The qRT-PCR results in Fig. 3a showed that, prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles could knockdown the expression of BRCAA1 gene in MGC803 cells after incubating with MGC803 cells for 48 h, in contrast, prepared FA-pRNA-3WJ-Scram siRNA nanoparticles could not knockdown the expression of BRCAA1 gene in MGC803 cells after incubation for 48 h, between two groups, there existed statistical difference (P < 0.01). Compared with BRCAA1 siRNA, prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles achieved similar silencing efficiency of BRCAA1 gene in MGC803 cells. The Ct, ΔCt, and ΔΔCt values for the qRT-PCR assay are shown in (supporting data). Additionally, as shown in Fig. 3b, Western blotting results further confirmed that prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles and BRCAA1 siRNA could down-regulate BRCAA1 expression in MGC803 cells, while prepared FA-pRNA-3WJ-Scram siRNA nanoparticles had little down-regulation of BRCAA1 protein expression in MGC803 cells, thus showing prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles can specifically reduce the expression of BRCAA1 protein in MGC803 cells. Importantly, the silencing potency was comparable to the Lipofectamine 2000 carried BRCAA1 siRNA group.


Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA.

Cui D, Zhang C, Liu B, Shu Y, Du T, Shu D, Wang K, Dai F, Liu Y, Li C, Pan F, Yang Y, Ni J, Li H, Brand-Saberi B, Guo P - Sci Rep (2015)

The BRCAA1 silencing effects of FA-pRNA-3WJ-BRCAA1siRNA assayed by (a) qRT-PCR (GADPH is the endogenous control)(there existed statistical difference between FA-pRNA-3WJ-BRCAA1siRNA group and FA-pRNA-3WJ-Scramb-siRNA group, P < 0.01) and (b) western blot assay (β-actin bands served as loading control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490273&req=5

f3: The BRCAA1 silencing effects of FA-pRNA-3WJ-BRCAA1siRNA assayed by (a) qRT-PCR (GADPH is the endogenous control)(there existed statistical difference between FA-pRNA-3WJ-BRCAA1siRNA group and FA-pRNA-3WJ-Scramb-siRNA group, P < 0.01) and (b) western blot assay (β-actin bands served as loading control).
Mentions: The qRT-PCR results in Fig. 3a showed that, prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles could knockdown the expression of BRCAA1 gene in MGC803 cells after incubating with MGC803 cells for 48 h, in contrast, prepared FA-pRNA-3WJ-Scram siRNA nanoparticles could not knockdown the expression of BRCAA1 gene in MGC803 cells after incubation for 48 h, between two groups, there existed statistical difference (P < 0.01). Compared with BRCAA1 siRNA, prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles achieved similar silencing efficiency of BRCAA1 gene in MGC803 cells. The Ct, ΔCt, and ΔΔCt values for the qRT-PCR assay are shown in (supporting data). Additionally, as shown in Fig. 3b, Western blotting results further confirmed that prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles and BRCAA1 siRNA could down-regulate BRCAA1 expression in MGC803 cells, while prepared FA-pRNA-3WJ-Scram siRNA nanoparticles had little down-regulation of BRCAA1 protein expression in MGC803 cells, thus showing prepared FA-pRNA-3WJ-BRCAA1 siRNA nanoparticles can specifically reduce the expression of BRCAA1 protein in MGC803 cells. Importantly, the silencing potency was comparable to the Lipofectamine 2000 carried BRCAA1 siRNA group.

Bottom Line: Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models.Apoptosis of gastric cancer cells was observed.All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

View Article: PubMed Central - PubMed

Affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

ABSTRACT
Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

No MeSH data available.


Related in: MedlinePlus