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

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical 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.

Ameres, S.L.; Zamore, P.D. Diversifying microRNA sequence and function. Nat. Rev. Mol. Cell Biol., 2013, 14(8), 475-488.
Seton-Rogers, S. Micrornas: Lines of communication. Nat. Rev. Cancer, 2012, 12, 580-581.
Adams, B.D.; Kasinski, A.L.; Slack, F.J. Aberrant regulation and function of MicroRNAs in cancer. Curr. Biol., 2014, 24(16), R762-R776.
Lu, J.; Getz, G.; Miska, E.A. MicroRNA expression profiles classify human cancers. Nature, 2005, 435(7043), 834-838.
Cheng, C.J.; Bahal, R.; Babar, I.A. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature, 2014, 518, 107-110.
Hayes, J.; Peruzzi, P.P.; Lawler, S. MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol. Med., 2014, 20(8), 460-469.
Fu, X.T.; Shi, Y.H.; Zhou, J.; Peng, Y.F.; Liu, W.R.; Shi, G.M.; Gao, Q.; Wang, X.Y.; Song, K.; Fan, J.; Ding, Z.B. MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in hepatocellular carcinoma. Cancer Lett., 2017, 412, 108-117.
D’Anzeo, M.; Faloppi, L.; Scartozzi, M. The role of Micro-RNAs in hepatocellular arcinoma: From molecular biology to treatment. Molecules, 2014, 19(5), 6393-6406.
Zhao, L.; Yu, H.; Yi, S. The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget, 2016, 7(29), 45370-45384.
Zheng, L.; Zhang, X.; Yang, F. Regulation of the P2X7R by microRNA-216b in human breast cancer. Biochem. Biophys. Res. Commun., 2014, 452(1), 197-204.
Zheng, J.; Wu, C.; Xu, Z. Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway. Mol. Cell. Biochem., 2015, 398(1), 1-9.
Song, M.; Park, Y.; Ryu, J. Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK. Toxicol. Appl. Pharmacol., 2013, 273(1), 130-139.
Song, H.; Sun, X.; Zhang, L. A preliminary analysis of association between the down -regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment. J. Psychiatr. Res., 2014, 54, 134-140.
Cilek, E.E.; Ozturk, H.; Gur Dedeoglu, B. Construction of miRNA-miRNA networks revealing the complexity of miRNA-mediated mechanisms in trastuzumab treated breast cancer cell lines. PLoS One, 2017, 12(10), e0185558.
Zhaohui, G. Jie, Yang.; Jingqiu, Li. Novel insights into the role of microRNA in lung cancer resistance to treatment and targeted therapy. Curr. Cancer Drug Targets, 2014, 14(3), 241-258.
Ping, L.; Xiaoming, L.; Yingyi, W. MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells. J. Biomed. Res., 2010, 24(6), 436-443.
Wang, B. M.S.; Shu-Hao Hsu, M.S.; Majumder, S. TGFβ mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene, 2010, 29(12), 1787-1797.
Ji, J.; Yamashita, T.; Wang, X.W. Wnt/beta-catenin signaling activates microRNA-181 expression in hepatocellular carcinoma. Cell Biosci., 2011, 1, 4.
Rimann, M.; Lühmann, T.; Textor, M. Characterization of PLL-g-PEG-DNA nanoparticles for the delivery of therapeutic DNA. Bioconjug. Chem., 2008, 19(2), 548-557.
Muddineti, O.S.; Ghosh, B.; Biswas, S. Current trends in using polymer coated gold nanoparticles for cancer therapy. Int. J. Pharm., 2015, 484(1), 252-267.
Kong, L.; Alves, C.S.; Hou, W. RGD peptide-modified dendrimer-entrapped gold nanoparticles enable highly efficient and specific gene delivery to stem cells. Acs. Appl. Mater. Inter., 2015, 7(8), 4833-4843.
You, Q.; Sun, Q.; Yu, M.; Wang, J.; Wang, S.; Liu, L.; Cheng, Y.; Wang, Y.; Song, Y.; Tan, F.; Li, N. BSA-bioinspired gadolinium hybrid-functionalized hollow gold nanoshells for NIRF/PA/CT/MR quadmodal diagnostic imaging guided photothermal/photodynamic cancer therapy. ACS Appl. Mater. Interfaces, 9(46), 40017-40030.
Wang, B.; Yu, X.; Wang, J. Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing. Biomaterials, 2016, 78, 27-39.
Ong, Z.Y.; Chen, S.; Nabavi, E.; Regoutz, A.; Payne, D.J.; Elson, D.S.; Dexter, D.T.; Dunlop, I.E. Multibranched gold nanoparticles with intrinsic LAT-1 targeting capabilities for selective photothermal therapy of breast cancer. ACS Appl. Mater. Interfaces, 2017, 9, 39259-39270.
Lin, M.; Gao, Y.; Hornicek, F. Near-infrared light activated delivery platform for cancer therapy. Adv. Colloid. Interface, 2015, 226, 123-137.
Song, W.; Du, J.; Sun, T. Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery. Small, 2010, 6(2), 239-246.
Dosio, F.; Arpicco, S.; Stella, B. Hyaluronic acid for anticancer drug and nucleic acid delivery. Adv. Drug Deliv. Rev., 2016, 97, 204-236.
Xia, Y.; Li, W.; Cobley, C.M. Gold nanocages: from synthesis to theranostic applications. Acc. Chem. Res., 2011, 44(10), 914-924.
Chen, J.; McLellan, J.M.; Siekkinen, A. Facile synthesis of gold−silver nanocages with controllable pores on the surface. J. Am. Chem. Soc., 2006, 128(46), 14776-14777.
Shen, J.; Kim, H.; Mu, C. Multifunctional gold nanorods for siRNA gene silencing and photothermal therapy. Adv. Healthc. Mater., 2014, 3(10), 1629-1637.
Lee, M.; Park, S.; Park, K. target-specific gene silencing of layer-by-layer assembled gold–cysteamine/siRNA/PEI/HA nanocomplex. ACS Nano, 2011, 5(8), 6138-6147.

Rights & PermissionsPrintExport Cite as

Article Details

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

Article Metrics

PDF: 25