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A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based Nanocarriers for Co-Delivery of Doxorubicin and siRNA.

Yin F, Yang C, Wang Q, Zeng S, Hu R, Lin G, Tian J, Hu S, Lan RF, Yoon HS, Lu F, Wang K, Yong KT - Theranostics (2015)

Bottom Line: The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells.Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments.The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore.

ABSTRACT
In this work, we report the engineering of polyelectrolyte polymers coated Gold nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small interfering RNA (siRNA) and an anticancer drug doxorubicin (DOX) to Panc-1 cancer cells for combination of both chemo- and siRNA-mediated mutant K-Ras gene silencing therapy. Superior anticancer efficacy was observed through synergistic combination of promoted siRNA and DOX release upon irradiating the nanoplex formulation with 665 nm light. Our antitumor study shows that the synergistic effect of AuNRs nanoplex formulation with 665 nm light treatment is able to inhibit the in vivo tumor volume growth rate by 90%. The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells. Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments. The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment.

No MeSH data available.


Related in: MedlinePlus

Gene expression evaluations of Panc-1 cells treated with different nanoparticle formulations of blank, AuNRs, DOX, siRNA, AuNRs/DOX/siRNA, AuNRs/DOX, AuNRs/siRNA and Lipo-siRNA. (A) mRNA relative expression levels detected by RT-PCR. (B) Protein relative expression levels detected by Western Blotting. Actin was used as the protein loading control for samples. Values are means ± SEM, n = 3; **, P < 0.01 vs Control, AuNRs and siRNA.
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Figure 5: Gene expression evaluations of Panc-1 cells treated with different nanoparticle formulations of blank, AuNRs, DOX, siRNA, AuNRs/DOX/siRNA, AuNRs/DOX, AuNRs/siRNA and Lipo-siRNA. (A) mRNA relative expression levels detected by RT-PCR. (B) Protein relative expression levels detected by Western Blotting. Actin was used as the protein loading control for samples. Values are means ± SEM, n = 3; **, P < 0.01 vs Control, AuNRs and siRNA.

Mentions: Following the flow cytometry analysis, we have examined the degree of K-Ras knockdown at the mRNA level and protein level for the Panc-1 cells treated with different formulations (Fig. 5 and Supplementary Fig. S1A). Both mRNA (Fig. 5A) and protein levels (Fig. 5B) of K-Ras are observed to decrease upon treating the Panc-1 cells with DOX, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA and Lipo/K-Ras siRNA formulation. Our result shows that no changes of K-Ras mRNA and protein levels are observed for the cells treated with either bared AuNRs,free K-Ras siRNA or scramble siRNA. However, when the DOX and K-Ras siRNA molecules are co-delivered into Panc-1 cells by using AuNRs-based nanocarriers, we observe a more effective inhibition rate of K-Ras expression than those formulations loaded with either DOX or K-Ras siRNA molecules. Thus, this indicates that the co-transfection of K-Ras siRNA and DOX by AuNRs is having a more pronounce effect for knocking down the pancreatic cancer growth markers. In addition, we have compared and studied the gene silencing efficiency between AuNRs/DOX/K-Ras siRNA nanoplex and Lipofectamine 2000-K-Ras siRNA formulation. Both Western Blotting analysis and RT-PCR analysis show that the AuNRs/DOX/K-Ras siRNA nanoplex formulation possesses a much higher efficiency in inhibiting the expression of K-Ras gene at the same siRNA dose when we compare it to Lipofectamine formulation.


A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based Nanocarriers for Co-Delivery of Doxorubicin and siRNA.

Yin F, Yang C, Wang Q, Zeng S, Hu R, Lin G, Tian J, Hu S, Lan RF, Yoon HS, Lu F, Wang K, Yong KT - Theranostics (2015)

Gene expression evaluations of Panc-1 cells treated with different nanoparticle formulations of blank, AuNRs, DOX, siRNA, AuNRs/DOX/siRNA, AuNRs/DOX, AuNRs/siRNA and Lipo-siRNA. (A) mRNA relative expression levels detected by RT-PCR. (B) Protein relative expression levels detected by Western Blotting. Actin was used as the protein loading control for samples. Values are means ± SEM, n = 3; **, P < 0.01 vs Control, AuNRs and siRNA.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4440440&req=5

Figure 5: Gene expression evaluations of Panc-1 cells treated with different nanoparticle formulations of blank, AuNRs, DOX, siRNA, AuNRs/DOX/siRNA, AuNRs/DOX, AuNRs/siRNA and Lipo-siRNA. (A) mRNA relative expression levels detected by RT-PCR. (B) Protein relative expression levels detected by Western Blotting. Actin was used as the protein loading control for samples. Values are means ± SEM, n = 3; **, P < 0.01 vs Control, AuNRs and siRNA.
Mentions: Following the flow cytometry analysis, we have examined the degree of K-Ras knockdown at the mRNA level and protein level for the Panc-1 cells treated with different formulations (Fig. 5 and Supplementary Fig. S1A). Both mRNA (Fig. 5A) and protein levels (Fig. 5B) of K-Ras are observed to decrease upon treating the Panc-1 cells with DOX, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA and Lipo/K-Ras siRNA formulation. Our result shows that no changes of K-Ras mRNA and protein levels are observed for the cells treated with either bared AuNRs,free K-Ras siRNA or scramble siRNA. However, when the DOX and K-Ras siRNA molecules are co-delivered into Panc-1 cells by using AuNRs-based nanocarriers, we observe a more effective inhibition rate of K-Ras expression than those formulations loaded with either DOX or K-Ras siRNA molecules. Thus, this indicates that the co-transfection of K-Ras siRNA and DOX by AuNRs is having a more pronounce effect for knocking down the pancreatic cancer growth markers. In addition, we have compared and studied the gene silencing efficiency between AuNRs/DOX/K-Ras siRNA nanoplex and Lipofectamine 2000-K-Ras siRNA formulation. Both Western Blotting analysis and RT-PCR analysis show that the AuNRs/DOX/K-Ras siRNA nanoplex formulation possesses a much higher efficiency in inhibiting the expression of K-Ras gene at the same siRNA dose when we compare it to Lipofectamine formulation.

Bottom Line: The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells.Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments.The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore.

ABSTRACT
In this work, we report the engineering of polyelectrolyte polymers coated Gold nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small interfering RNA (siRNA) and an anticancer drug doxorubicin (DOX) to Panc-1 cancer cells for combination of both chemo- and siRNA-mediated mutant K-Ras gene silencing therapy. Superior anticancer efficacy was observed through synergistic combination of promoted siRNA and DOX release upon irradiating the nanoplex formulation with 665 nm light. Our antitumor study shows that the synergistic effect of AuNRs nanoplex formulation with 665 nm light treatment is able to inhibit the in vivo tumor volume growth rate by 90%. The antitumor effect is contributed from the inactivation of K-Ras gene and thereby causing a profound synthesis (S) phase arrest in treated Panc-1 cells. Our study shows that the percentage of Panc-1 cells treated by nanoplex formulation with S phase is determined to be 35% and it is 17% much higher than that of Panc-1 cells without any treatments. The developed nanotherapy formulation here, that combines chemotherapy, RNA silencing and NIR window light-mediated therapy, will be seen to be the next natural step to be taken in the clinical research for improving the therapeutic outcomes of the pancreatic adenocarcinoma treatment.

No MeSH data available.


Related in: MedlinePlus