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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

Fluorescent images of Panc-1 cells treated with different nanocomplex formulations four hours after treatment. (A) PBS as blank control, (B) free siRNAFAM as negative control, (C) and (D)AuNRs/DOX/siRNAFAM with different volume ratio of AuNRs (OD = 2): DOX(1 mg/mL): siRNAFAM (8.125 nmol/mL) = 10:1:2 or 10:1:3, respectively and (E) Lipofectamine 2000 conjugated siRNAFAM as positive control. The cell nucleus is stained with DAPI (pseudo-colored in blue) and signals from FAM and DOX are assigned in green and red, respectively.
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Figure 3: Fluorescent images of Panc-1 cells treated with different nanocomplex formulations four hours after treatment. (A) PBS as blank control, (B) free siRNAFAM as negative control, (C) and (D)AuNRs/DOX/siRNAFAM with different volume ratio of AuNRs (OD = 2): DOX(1 mg/mL): siRNAFAM (8.125 nmol/mL) = 10:1:2 or 10:1:3, respectively and (E) Lipofectamine 2000 conjugated siRNAFAM as positive control. The cell nucleus is stained with DAPI (pseudo-colored in blue) and signals from FAM and DOX are assigned in green and red, respectively.

Mentions: The cellular uptake efficiency and intracellular distribution of DOX and siRNAFAM are monitored using fluorescence microscopy as shown in Figure 3. The Panc-1 cells are treated with various AuNRs nanoplex formulations for 4 hours before examining them under the microscope. The observed fluorescence signals of DOX and FAM in Figure 3C and 3D demonstrate that DOX and siRNA have been successfully co-delivered into the tumor cells by using the PSS and PAH-coated AuNRs. No FAM signals are observed from the cells treated with free siRNAFAM (Fig. 3D) and this suggests that the naked siRNA molecules are incapable of penetrating the cell membrane due to their negative charging nature and fast degradation in biological fluid environment. The positive control study (Fig. 3E) shows that the tumor cells can be transfected with siRNAFAM by using commercially available transfection reagent Lipofectamine 2000. These experiments indicate that there are almost no obvious differences in the delivery efficiency for both AuNRs nanoplex and Lipofectamine 2000 formulations and the use of AuNRs nanoplex can effectively protect siRNA from fast degradation which is consistent with our previous findings 28.


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)

Fluorescent images of Panc-1 cells treated with different nanocomplex formulations four hours after treatment. (A) PBS as blank control, (B) free siRNAFAM as negative control, (C) and (D)AuNRs/DOX/siRNAFAM with different volume ratio of AuNRs (OD = 2): DOX(1 mg/mL): siRNAFAM (8.125 nmol/mL) = 10:1:2 or 10:1:3, respectively and (E) Lipofectamine 2000 conjugated siRNAFAM as positive control. The cell nucleus is stained with DAPI (pseudo-colored in blue) and signals from FAM and DOX are assigned in green and red, respectively.
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Related In: Results  -  Collection

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Figure 3: Fluorescent images of Panc-1 cells treated with different nanocomplex formulations four hours after treatment. (A) PBS as blank control, (B) free siRNAFAM as negative control, (C) and (D)AuNRs/DOX/siRNAFAM with different volume ratio of AuNRs (OD = 2): DOX(1 mg/mL): siRNAFAM (8.125 nmol/mL) = 10:1:2 or 10:1:3, respectively and (E) Lipofectamine 2000 conjugated siRNAFAM as positive control. The cell nucleus is stained with DAPI (pseudo-colored in blue) and signals from FAM and DOX are assigned in green and red, respectively.
Mentions: The cellular uptake efficiency and intracellular distribution of DOX and siRNAFAM are monitored using fluorescence microscopy as shown in Figure 3. The Panc-1 cells are treated with various AuNRs nanoplex formulations for 4 hours before examining them under the microscope. The observed fluorescence signals of DOX and FAM in Figure 3C and 3D demonstrate that DOX and siRNA have been successfully co-delivered into the tumor cells by using the PSS and PAH-coated AuNRs. No FAM signals are observed from the cells treated with free siRNAFAM (Fig. 3D) and this suggests that the naked siRNA molecules are incapable of penetrating the cell membrane due to their negative charging nature and fast degradation in biological fluid environment. The positive control study (Fig. 3E) shows that the tumor cells can be transfected with siRNAFAM by using commercially available transfection reagent Lipofectamine 2000. These experiments indicate that there are almost no obvious differences in the delivery efficiency for both AuNRs nanoplex and Lipofectamine 2000 formulations and the use of AuNRs nanoplex can effectively protect siRNA from fast degradation which is consistent with our previous findings 28.

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