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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

Antitumor activity of AuNRs/DOX/K-Ras siRNA in a Panc-1 xenograft animal model. (A) Representative images of mouse and tumor tissues treated with (1) PBS, (2) free AuNRs, (3) free DOX, (4) AuNRs/DOX, (5) AuNRs/siRNA, (6) AuNRs/DOX/siRNA or (7) AuNRs/DOX/siRNA with 665 nm light irradiation. For mice treated with both AuNRs/DOX/siRNA and 665 nm light, the strongest inhibition rate was observed. (B) Relative changes in tumor volume versus time for mice treated by PBS, free AuNRs, free DOX, AuNRs/DOX, AuNRs/siRNA, AuNRs/DOX/siRNA or AuNRs/DOX/siRNA with 665 nm light, respectively. Relative tumor volume was defined as (V-V0)/ V0, where V and V0 indicate the tumor volume on a particular day and day 0, respectively. Error bars represent SEMs for triplicate data. Mean tumor volumes were analyzed using one-way ANOVA. *, P < 0.05, **, P < 0.01 (n=5-7 tumors).
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Figure 10: Antitumor activity of AuNRs/DOX/K-Ras siRNA in a Panc-1 xenograft animal model. (A) Representative images of mouse and tumor tissues treated with (1) PBS, (2) free AuNRs, (3) free DOX, (4) AuNRs/DOX, (5) AuNRs/siRNA, (6) AuNRs/DOX/siRNA or (7) AuNRs/DOX/siRNA with 665 nm light irradiation. For mice treated with both AuNRs/DOX/siRNA and 665 nm light, the strongest inhibition rate was observed. (B) Relative changes in tumor volume versus time for mice treated by PBS, free AuNRs, free DOX, AuNRs/DOX, AuNRs/siRNA, AuNRs/DOX/siRNA or AuNRs/DOX/siRNA with 665 nm light, respectively. Relative tumor volume was defined as (V-V0)/ V0, where V and V0 indicate the tumor volume on a particular day and day 0, respectively. Error bars represent SEMs for triplicate data. Mean tumor volumes were analyzed using one-way ANOVA. *, P < 0.05, **, P < 0.01 (n=5-7 tumors).

Mentions: To assess whether AuNRs nanoplex formulations exhibits anti-tumor activities in animals, we have examined the effects of nanoplex in the tumor-bearing mice (Fig. 10). A significant reduction of tumor volume is observed for the mice treated with AuNRs/DOX/K-Ras siRNA nanoplex (Fig. 10A-6). Moreover, the combination of AuNRs/DOX/K-Ras siRNA nanoplex formulation and 665 nm light treatment (Fig. 10A-7) provides the strongest effect in suppressing the tumor growth in vivo. Tumors bearing mice treated with either PBS (Fig. 10A-1) or AuNRs (Fig. 10A-2) formulations do not show any signs of tumor growth suppression. Instead, the tumor size increases by 25 folds over the period from day 1 to 25. AuNRs/K-Ras siRNA nanoplex (Fig. 10A-5), DOX formulation (Fig. 10A-3), AuNRs/DOX nanoplex (Fig. 10A-4) and AuNRs with 665 nm light (Supplementary Fig. S4), all these treatments are able to show some effectiveness in suppressing the tumor growth for the first few days and but thereafter the tumor size start to increase and it reaches up to 15 folds of the original tumor size at the end of our evaluation study.


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)

Antitumor activity of AuNRs/DOX/K-Ras siRNA in a Panc-1 xenograft animal model. (A) Representative images of mouse and tumor tissues treated with (1) PBS, (2) free AuNRs, (3) free DOX, (4) AuNRs/DOX, (5) AuNRs/siRNA, (6) AuNRs/DOX/siRNA or (7) AuNRs/DOX/siRNA with 665 nm light irradiation. For mice treated with both AuNRs/DOX/siRNA and 665 nm light, the strongest inhibition rate was observed. (B) Relative changes in tumor volume versus time for mice treated by PBS, free AuNRs, free DOX, AuNRs/DOX, AuNRs/siRNA, AuNRs/DOX/siRNA or AuNRs/DOX/siRNA with 665 nm light, respectively. Relative tumor volume was defined as (V-V0)/ V0, where V and V0 indicate the tumor volume on a particular day and day 0, respectively. Error bars represent SEMs for triplicate data. Mean tumor volumes were analyzed using one-way ANOVA. *, P < 0.05, **, P < 0.01 (n=5-7 tumors).
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Figure 10: Antitumor activity of AuNRs/DOX/K-Ras siRNA in a Panc-1 xenograft animal model. (A) Representative images of mouse and tumor tissues treated with (1) PBS, (2) free AuNRs, (3) free DOX, (4) AuNRs/DOX, (5) AuNRs/siRNA, (6) AuNRs/DOX/siRNA or (7) AuNRs/DOX/siRNA with 665 nm light irradiation. For mice treated with both AuNRs/DOX/siRNA and 665 nm light, the strongest inhibition rate was observed. (B) Relative changes in tumor volume versus time for mice treated by PBS, free AuNRs, free DOX, AuNRs/DOX, AuNRs/siRNA, AuNRs/DOX/siRNA or AuNRs/DOX/siRNA with 665 nm light, respectively. Relative tumor volume was defined as (V-V0)/ V0, where V and V0 indicate the tumor volume on a particular day and day 0, respectively. Error bars represent SEMs for triplicate data. Mean tumor volumes were analyzed using one-way ANOVA. *, P < 0.05, **, P < 0.01 (n=5-7 tumors).
Mentions: To assess whether AuNRs nanoplex formulations exhibits anti-tumor activities in animals, we have examined the effects of nanoplex in the tumor-bearing mice (Fig. 10). A significant reduction of tumor volume is observed for the mice treated with AuNRs/DOX/K-Ras siRNA nanoplex (Fig. 10A-6). Moreover, the combination of AuNRs/DOX/K-Ras siRNA nanoplex formulation and 665 nm light treatment (Fig. 10A-7) provides the strongest effect in suppressing the tumor growth in vivo. Tumors bearing mice treated with either PBS (Fig. 10A-1) or AuNRs (Fig. 10A-2) formulations do not show any signs of tumor growth suppression. Instead, the tumor size increases by 25 folds over the period from day 1 to 25. AuNRs/K-Ras siRNA nanoplex (Fig. 10A-5), DOX formulation (Fig. 10A-3), AuNRs/DOX nanoplex (Fig. 10A-4) and AuNRs with 665 nm light (Supplementary Fig. S4), all these treatments are able to show some effectiveness in suppressing the tumor growth for the first few days and but thereafter the tumor size start to increase and it reaches up to 15 folds of the original tumor size at the end of our evaluation study.

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