Co-delivery of GOLPH3 siRNA and gefitinib by cationic lipid-PLGA nanoparticles improves EGFR-targeted therapy for glioma

  • Chengkun Ye
  • Bomin Pan
  • Haoyue Xu
  • Zongren Zhao
  • Jiawei Shen
  • Jun Lu
  • Rutong Yu
  • Hongmei LiuEmail author
Original Article


Glioblastoma is one of the most aggressive types of brain tumor. Epidermal growth factor receptors (EGFRs) are overexpressed in glioma, and EGFR amplifications and mutations lead to rapid proliferation and invasion. EGFR-targeted therapy might be an effective treatment for glioma. Gefitinib (Ge) is an EGFR tyrosine kinase inhibitor (TKI), and Golgi phosphoprotein 3 (GOLPH3) expression is associated with worse glioma prognosis. Downregulation of GOLPH3 could promote EGFR degradation. Here, an angiopep-2 (A2)-modified cationic lipid-poly (lactic-co-glycolic acid) (PLGA) nanoparticle (A2-N) was developed that can release Ge and GOLPH3 siRNA (siGOLPH3) upon entering glioma cells and therefore acts as a combinatorial anti-tumor therapy. The in vitro and in vivo studies proved that A2-N/Ge/siGOLPH3 successfully crossed the blood-brain barrier (BBB) and targeted glioma. Released siGOLPH3 effectively silenced GOLPH3 mRNA expression and further promoted EGFR and p-EGFR degradation. Released Ge also markedly inhibited EGFR signaling. This combined EGFR-targeted action achieved remarkable anti-glioma effects and could be a safe and effective treatment for glioma.

Key messages

  • Angiopep-2-modified cationic lipid polymer can penetrate the BBB.

  • Gefitinib can inhibit EGFR signaling and block the autophosphorylation of critical tyrosine residues on EGFR.

  • GOLPH3 siRNA can be transfected into glioma and downregulate GLOPH3 expression.

  • A2-N/Ge/siGOLPH3 can inhibit glioma growth.


Glioma Nanoparticles EGFR GOLPH3 Gefitinib 





adenosine triphosphate


blood-brain barrier


cationic liposomes


confocal laser scan microscopy


4′, 6-diamidino-2-phenylindole dihydrochloride


dimethyl sulfoxide


Dulbecco’s Modified Eagle’s Medium


1, 2-Dioleoyl-3-trimethylammonium-propane




Ethidium Bromide




epidermal growth factor receptor


epidermal growth factor receptor variant typeIII


enhanced permeability and retention


fetal bovine serum


glioblastoma multiforme




golgi phosphoprotein 3




intravenous injection


monoclonal antibodies


low-density lipoprotein receptor-related protein-1




nonsense siRNA




optical density


phosphate buffer saline


poly (D, L-lactic-co-glycolic acid)


quantitative real-time polymerase chain reaction


receptor mediated transcytosis


RNA interference




small interfering RNA


The Cancer Genome Atlas


transmission electron microscopy


tyrosine kinase inhibitors


western blot




Funding information

This work was financially supported by National Natural Science Foundation of China (Grant No. 81772665), Jiangsu Province, Key Research & Development Plan of Jiangsu Province (No. BE2016646), Jiangsu provincial Commission of Health and Family Planning (Grant No. Q201608), Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant No. KYCX18_2197), and Six Talents Peak Foundation of Jiangsu Province (No. 2018-WSW-071).

Compliance with ethical standards

Ethics approval and consent to participate

This study was performed according to the guidelines for the Care and Use of Laboratory Animals and the animal experimental protocols were approved by Xuzhou Medical University of China Animal Care and Use Committee.

Competing interests

The authors declare that they have no competing interests.

Supplementary material

109_2019_1843_MOESM1_ESM.docx (1.1 mb)
ESM 1 (DOCX 1087 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chengkun Ye
    • 1
    • 2
  • Bomin Pan
    • 1
    • 2
  • Haoyue Xu
    • 1
    • 2
  • Zongren Zhao
    • 1
    • 2
  • Jiawei Shen
    • 1
    • 2
  • Jun Lu
    • 3
  • Rutong Yu
    • 1
    • 2
  • Hongmei Liu
    • 1
    • 2
    Email author
  1. 1.Institute of Nervous System DiseasesXuzhou Medical UniversityXuzhouChina
  2. 2.Department of NeurosurgeryAffiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  3. 3.Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life ScienceJiangsu Normal UniversityXuzhouChina

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