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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

Characterization of AuNRs and schematic illustration of the engineered AuNRs-based nanocarriers. (A) Absorption spectra of the AuNRs, where two peaks were observed locating at 517 nm and 620 nm for transverse and longitudinal localized surface plasmon resonances, respectively. (B) Hydrodynamic size distribution of the AuNRs with an average size centered at 24.9±2.15 nm. (C) TEM images of the AuNRs. (1) and (2) are AuNRs as synthesized, (3) AuNRs coated with PSS (poly-sodium 4-styrenesulfonate) and (4) AuNRs coated with PSS and PAH (poly-allylamine hydrochloride). (D) Schematic illustration of layer-by-layer assembling of AuNRs loading with DOX and siRNA (see experimental section for details).
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Figure 1: Characterization of AuNRs and schematic illustration of the engineered AuNRs-based nanocarriers. (A) Absorption spectra of the AuNRs, where two peaks were observed locating at 517 nm and 620 nm for transverse and longitudinal localized surface plasmon resonances, respectively. (B) Hydrodynamic size distribution of the AuNRs with an average size centered at 24.9±2.15 nm. (C) TEM images of the AuNRs. (1) and (2) are AuNRs as synthesized, (3) AuNRs coated with PSS (poly-sodium 4-styrenesulfonate) and (4) AuNRs coated with PSS and PAH (poly-allylamine hydrochloride). (D) Schematic illustration of layer-by-layer assembling of AuNRs loading with DOX and siRNA (see experimental section for details).

Mentions: In our experiments, 5 types of AuNRs based nanoplex formulations are prepared for positive, negative and control studies: (i) negatively charged AuNRs/PSS formulation where the particles surface are modified with PSS polymer; (ii) positively charged AuNRs/PSS/PAH formulation where AuNRs/PSS particles are functionalized with PAH polymer; (iii) AuNRs/DOX formulation where AuNRs/PSS particles are loaded with DOX molecules and thereafter modified with PAH polymer; (iv) AuNRs/siRNA formulation is prepared where the AuNRs/PSS/PAH particles are used to bind with siRNA molecules; (v) AuNRs/DOX/siRNA formulation herein refers to the AuNRs/PSS/DOX/PAH particles are used to be functionalized with siRNA molecules (Supplementary Table S1; Fig. 1D).


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)

Characterization of AuNRs and schematic illustration of the engineered AuNRs-based nanocarriers. (A) Absorption spectra of the AuNRs, where two peaks were observed locating at 517 nm and 620 nm for transverse and longitudinal localized surface plasmon resonances, respectively. (B) Hydrodynamic size distribution of the AuNRs with an average size centered at 24.9±2.15 nm. (C) TEM images of the AuNRs. (1) and (2) are AuNRs as synthesized, (3) AuNRs coated with PSS (poly-sodium 4-styrenesulfonate) and (4) AuNRs coated with PSS and PAH (poly-allylamine hydrochloride). (D) Schematic illustration of layer-by-layer assembling of AuNRs loading with DOX and siRNA (see experimental section for details).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4440440&req=5

Figure 1: Characterization of AuNRs and schematic illustration of the engineered AuNRs-based nanocarriers. (A) Absorption spectra of the AuNRs, where two peaks were observed locating at 517 nm and 620 nm for transverse and longitudinal localized surface plasmon resonances, respectively. (B) Hydrodynamic size distribution of the AuNRs with an average size centered at 24.9±2.15 nm. (C) TEM images of the AuNRs. (1) and (2) are AuNRs as synthesized, (3) AuNRs coated with PSS (poly-sodium 4-styrenesulfonate) and (4) AuNRs coated with PSS and PAH (poly-allylamine hydrochloride). (D) Schematic illustration of layer-by-layer assembling of AuNRs loading with DOX and siRNA (see experimental section for details).
Mentions: In our experiments, 5 types of AuNRs based nanoplex formulations are prepared for positive, negative and control studies: (i) negatively charged AuNRs/PSS formulation where the particles surface are modified with PSS polymer; (ii) positively charged AuNRs/PSS/PAH formulation where AuNRs/PSS particles are functionalized with PAH polymer; (iii) AuNRs/DOX formulation where AuNRs/PSS particles are loaded with DOX molecules and thereafter modified with PAH polymer; (iv) AuNRs/siRNA formulation is prepared where the AuNRs/PSS/PAH particles are used to bind with siRNA molecules; (v) AuNRs/DOX/siRNA formulation herein refers to the AuNRs/PSS/DOX/PAH particles are used to be functionalized with siRNA molecules (Supplementary Table S1; Fig. 1D).

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