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

Author(s): Li-Juan Yan , Xin-Hong Guo , Wei-Ping Wang , Yu-Rong Hu* , Shao-Feng Duan* , Ying Liu , Zhi Sun , Sheng-Nan Huang , Hui-li Li .

Journal Name: Current Cancer Drug Targets

Volume 19 , Issue 4 , 2019

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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.

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Article Details

VOLUME: 19
ISSUE: 4
Year: 2019
Page: [330 - 337]
Pages: 8
DOI: 10.2174/1568009618666181016144855
Price: $58

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