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Gene Therapy and Photothermal Therapy of Layer-by-Layer Assembled AuNCs /PEI/miRNA/ HA Nanocomplexes

[ Vol. 19 , Issue. 4 ]

Author(s):

Li-Juan Yan, Xin-Hong Guo, Wei-Ping Wang, Yu-Rong Hu*, Shao-Feng Duan*, Ying Liu, Zhi Sun, Sheng-Nan Huang and Hui-li LiPages 330-337 (8)

Abstract:


Background: MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability.

Methods: In this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis.

Results: The results of UV spectra, hydrodynamic diameter and zeta potential analyses confirmed the formation of AuNCs/PEI/ miRNA/HA complex with its average particle size of ca. 153 nm and surface charge of ca. -9.43 mV. Next, we evaluated the antitumor effect of the nanocomplex mediated by the combination of gene therapy and photothermal therapy (PTT) against hepatocellular carcinoma (HCC) in vitro.

Conclusion: Our experimental results indicated that the AuNCs/PEI/miRNA/HA complex effectively delivered miRNA to the target cells and its antitumor effect was significantly enhanced by the combination of gene therapy and photothermal therapy. In addition, anti-miR-181b could promote Bel-7402 cell arrest in S phase and improve TIMP-3 mRNA expression. All these results suggested that AuNCs/PEI/miRNA/HA gene delivery system with combination of gene therapy and photothermal therapy might be exploited for HCC treatment.

Keywords:

Hepatocellular carcinoma, MicroRNA, gold nanocages, photothermal therapy, hyaluronic acid, targeted delivery.

Affiliation:

Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Henan International Joint Laboratory for Nuclear Protein Regulation, School of Medical Sciences, Henan University, N. Jinming Ave., Kaifeng, Henan 475004, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Henan International Joint Laboratory for Nuclear Protein Regulation, School of Medical Sciences, Henan University, N. Jinming Ave., Kaifeng, Henan 475004, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province; School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001

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