Limits...
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

Cell viability test of different formulations. (A) The growth of Panc-1 cells was inhibited by AuNRs/DOX with 665 nm light. Panc-1 cells were treated with PBS, 2 μg/mL DOX in PBS, 2 μg/mL DOX loaded in PSS/AuNRs for 4 hours (1), then changed fresh medium with 10% FBS, the cells transfected with AuNRs/DOX were treated with 665 nm light or not, all the cells incubated for additional 20 hours (2). (B) Cytotoxicity study of AuNRs where Panc-1 cells were treated with different concentrations of AuNRs/PSS/PAH for 48 hours. (C) Panc-1 cells were treated with AuNRs, DOX, K-Ras siRNA, Lipo-K-Ras siRNA, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA (with or without NIR) at DOX concentration of 2 μg/mL and K-Ras siRNA concentration of 20 μM for 12, 24, 48, and 72 hours. Data are presented as the mean±SEM of triplicate experiments.*, P < 0.05, **, P < 0.01 vs Control, AuNRs and siRNA.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4440440&req=5

Figure 9: Cell viability test of different formulations. (A) The growth of Panc-1 cells was inhibited by AuNRs/DOX with 665 nm light. Panc-1 cells were treated with PBS, 2 μg/mL DOX in PBS, 2 μg/mL DOX loaded in PSS/AuNRs for 4 hours (1), then changed fresh medium with 10% FBS, the cells transfected with AuNRs/DOX were treated with 665 nm light or not, all the cells incubated for additional 20 hours (2). (B) Cytotoxicity study of AuNRs where Panc-1 cells were treated with different concentrations of AuNRs/PSS/PAH for 48 hours. (C) Panc-1 cells were treated with AuNRs, DOX, K-Ras siRNA, Lipo-K-Ras siRNA, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA (with or without NIR) at DOX concentration of 2 μg/mL and K-Ras siRNA concentration of 20 μM for 12, 24, 48, and 72 hours. Data are presented as the mean±SEM of triplicate experiments.*, P < 0.05, **, P < 0.01 vs Control, AuNRs and siRNA.

Mentions: We have also examined the states of cell growth where they are treated with AuNRs nanoplex and 665 nm light (Fig. 9A). In this study, Panc-1 cells are treated with PBS, AuNRs, DOX, AuNRs/DOX/K-Ras siRNA nanoplex formulation for 4 hours. After that, the cells treated with AuNRs/DOX/K-Ras siRNA nanoplex are exposed under 665 nm light for 10 minutes and all these cells are then cultured for 20 hours prior performing imaging analysis. Using white field imaging, the cells treated with both AuNRs/DOX/K-Ras siRNA nanoplex formulation and 665 nm light display the most serious inhibition and the apoptosis of cells are observed for the examined sample. Therefore, these control release experiments clearly indicate that light-driven drug delivery system that is based on AuNRs nanoplex is an effective approach to deliver and release desired therapy agents to tumor cells.


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)

Cell viability test of different formulations. (A) The growth of Panc-1 cells was inhibited by AuNRs/DOX with 665 nm light. Panc-1 cells were treated with PBS, 2 μg/mL DOX in PBS, 2 μg/mL DOX loaded in PSS/AuNRs for 4 hours (1), then changed fresh medium with 10% FBS, the cells transfected with AuNRs/DOX were treated with 665 nm light or not, all the cells incubated for additional 20 hours (2). (B) Cytotoxicity study of AuNRs where Panc-1 cells were treated with different concentrations of AuNRs/PSS/PAH for 48 hours. (C) Panc-1 cells were treated with AuNRs, DOX, K-Ras siRNA, Lipo-K-Ras siRNA, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA (with or without NIR) at DOX concentration of 2 μg/mL and K-Ras siRNA concentration of 20 μM for 12, 24, 48, and 72 hours. Data are presented as the mean±SEM of triplicate experiments.*, P < 0.05, **, P < 0.01 vs Control, AuNRs and siRNA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4440440&req=5

Figure 9: Cell viability test of different formulations. (A) The growth of Panc-1 cells was inhibited by AuNRs/DOX with 665 nm light. Panc-1 cells were treated with PBS, 2 μg/mL DOX in PBS, 2 μg/mL DOX loaded in PSS/AuNRs for 4 hours (1), then changed fresh medium with 10% FBS, the cells transfected with AuNRs/DOX were treated with 665 nm light or not, all the cells incubated for additional 20 hours (2). (B) Cytotoxicity study of AuNRs where Panc-1 cells were treated with different concentrations of AuNRs/PSS/PAH for 48 hours. (C) Panc-1 cells were treated with AuNRs, DOX, K-Ras siRNA, Lipo-K-Ras siRNA, AuNRs/K-Ras siRNA, AuNRs/DOX/K-Ras siRNA (with or without NIR) at DOX concentration of 2 μg/mL and K-Ras siRNA concentration of 20 μM for 12, 24, 48, and 72 hours. Data are presented as the mean±SEM of triplicate experiments.*, P < 0.05, **, P < 0.01 vs Control, AuNRs and siRNA.
Mentions: We have also examined the states of cell growth where they are treated with AuNRs nanoplex and 665 nm light (Fig. 9A). In this study, Panc-1 cells are treated with PBS, AuNRs, DOX, AuNRs/DOX/K-Ras siRNA nanoplex formulation for 4 hours. After that, the cells treated with AuNRs/DOX/K-Ras siRNA nanoplex are exposed under 665 nm light for 10 minutes and all these cells are then cultured for 20 hours prior performing imaging analysis. Using white field imaging, the cells treated with both AuNRs/DOX/K-Ras siRNA nanoplex formulation and 665 nm light display the most serious inhibition and the apoptosis of cells are observed for the examined sample. Therefore, these control release experiments clearly indicate that light-driven drug delivery system that is based on AuNRs nanoplex is an effective approach to deliver and release desired therapy agents to tumor cells.

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