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

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...

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Published inTheranostics Vol. 5; no. 8; pp. 818 - 833
Main Authors Yin, Feng, Yang, Chengbin, Wang, Qianqian, Zeng, Shuwen, Hu, Rui, Lin, Guimiao, Tian, Jinglin, Hu, Siyi, Lan, Rong Feng, Yoon, Ho Sup, Lu, Fei, Wang, Kuan, Yong, Ken-Tye
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Published Australia Ivyspring International Publisher 01.01.2015
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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.
AbstractList 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.
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.
Author Wang, Qianqian
Yin, Feng
Hu, Rui
Lan, Rong Feng
Hu, Siyi
Zeng, Shuwen
Wang, Kuan
Tian, Jinglin
Yoon, Ho Sup
Lu, Fei
Yang, Chengbin
Yong, Ken-Tye
Lin, Guimiao
AuthorAffiliation 2. Division of Structural Biology & Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore
7. School of Science, Changchun University of Science and Technology, Changchun, 130022, China
3. Laboratory of Chemical Genetics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
8. Institute of Research and Continuing Education, Hong Kong Baptist University (Shenzhen), Shenzhen 518057, China
5. The key lab of Biomedical Engineering and Research Institute of Uropoiesis and Reproduction, School of Medical Sciences, Shenzhen University, Shenzhen, 518060, China
1. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore
4. Nanomedicine Program and Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan
6. CINTRA CNRS/NTU/THALES, UMI 3288, Research Techno Plaza, 50 Nanyang Drive, Border X Block, Singapore, 637553
9.
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26000055$$D View this record in MEDLINE/PubMed
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Copyright 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. 2015
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Keywords Pancreatic adenocarcinoma
AuNRs
tumors
siRNA
K-Ras
Doxorubicin
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Notes Competing Interests: The authors have declared that no competing interest exists.
These authors contributed equally to this work
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Snippet In this work, we report the engineering of polyelectrolyte polymers coated Gold nanorods (AuNRs)-based nanocarriers that are capable of co-delivering small...
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StartPage 818
SubjectTerms Adenocarcinoma - drug therapy
Animals
Antineoplastic Agents - administration & dosage
Cell Line, Tumor
Cell Survival - drug effects
Disease Models, Animal
Doxorubicin - administration & dosage
Drug Carriers - administration & dosage
Female
Gold - administration & dosage
Humans
Hyperthermia, Induced - methods
Light
Mice, Nude
Nanotubes
Pancreatic Neoplasms - drug therapy
Phototherapy - methods
Research Paper
RNA, Small Interfering - administration & dosage
Treatment Outcome
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Title A Light-Driven Therapy of Pancreatic Adenocarcinoma Using Gold Nanorods-Based Nanocarriers for Co-Delivery of Doxorubicin and siRNA
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