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

• Published in: Theranostics 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
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01.01.2015
• Subjects: 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; Pancreatic adenocarcinoma; AuNRs; tumors; siRNA; K-Ras; Doxorubicin
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.11335

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.