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.