Top

Published in:

01-11-2018 | Laboratory Investigation

Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes

Authors: Zixuan Yuan, Liang Zhao, Yafei Zhang, Shun Li, Bomin Pan, Lei Hua, Zhen Wang, Chengkun Ye, Jun Lu, Rutong Yu, Hongmei Liu

Published in: Journal of Neuro-Oncology | Issue 2/2018

Abstract

Purpose

GOLPH3 has been shown to be involved in glioma proliferation. In this study, we aimed to demonstrate that GOLPH3 can serve as a target for glioma gene therapy.

Methods

During the experiment, cationic liposomes with angiopep-2 (A2-CL) were used to deliver siGOLPH3 crossing the blood–brain barrier and reaching the glioma.

Results

At the cellular level, the A2-CL/siGOLPH3 could silence GOLPH3 and then effectively inhibited the proliferation of cells. In vivo experiments, using U87-GFP-Luci-bearing BALB/c mouse models, we demonstrated that A2-CL could deliver GOLPH3-siRNA specifically to glioma and effectively inhibit glioma growth.

Conclusions

This study shows that GOLPH3 has great potential as a target for the gene therapy of glioma and is of great value in precise medical applications.

Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507CrossRefPubMed

Sukhdeo K, Hambardzumyan D, Rich JN (2011) Glioma development: where did it all go wrong? Cell 146:187–188CrossRefPubMed

Jain RK, Di TE, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT (2007) Angiogenesis in brain tumours. Nat Rev Neurosci 8:610–622CrossRefPubMed

Bumcrot D, Manoharan M, Koteliansky V, Sah DWY (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2:711–719CrossRefPubMed

Rietwyk S, Peer D (2017) Next-generation lipids in RNA interference therapeutics. ACS Nano 11:7572–7586CrossRefPubMed

Dowdy SF (2017) Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol 35:222–229CrossRefPubMed

Cohen ZR, Ramishetti S, Peshesyaloz N, Goldsmith M, Wohl A, Zibly Z, Peer D (2015) Localized RNAi therapeutics of chemo-resistant grade IV glioma using hyaluronan-grafted lipid-based nanoparticles. ACS Nano 9:1581–1591CrossRefPubMed

Zhou J, Xu T, Qin R, Yan Y, Chen C, Chen Y, Yu H, Xia C, Lu Y, Ding X (2012) Overexpression of golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis. J Neurooncol 110:195–203CrossRefPubMed

Buschman MD, Rahajeng J, Field SJ (2015) GOLPH3 links the golgi, DNA damage, and cancer. Can Res 75:624–627CrossRef

10.

Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T (2009) GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 459:1085–1090CrossRefPubMedPubMedCentral

11.

Zhou X, Xie S, Wu S, Qi Y, Wang Z, Zhang H, Dong L, Wang X, Yu D, Liu G (2017) Golgi phosphoprotein 3 promotes glioma progression via inhibiting Rab5-mediated endocytosis and degradation of epidermal growth factor receptor. Neuro Oncol 19(12):1628–1639CrossRefPubMedPubMedCentral

12.

Boado RJ (2007) Blood–brain barrier transport of non-viral gene and RNAi therapeutics. Pharm Res 24:1772–1787CrossRefPubMed

13.

Podesta JE, Al-Jamal KT, Herrero MA, Tian B, Ali-Boucetta H, Hegde V, Bianco A, Prato M, Kostarelos K (2010) Antitumor activity and prolonged survival by carbon-nanotube-mediated therapeutic siRNA silencing in a human lung xenograft model. Small 5:1176–1185

14.

Lv H, Zhang S, Wang B, Cui S, Yan J (2006) Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 114:100–109CrossRefPubMed

15.

Oller-Salvia B, Sanchez-Navarro M, Giralt E, Teixido M (2016) ChemInform abstract: blood—brain barrier shuttle peptides: an emerging paradigm for brain delivery. Chem Soc Rev 47:4690–4707CrossRef

16.

Cho CF, Wolfe JM, Fadzen CM, Calligaris D, Hornburg K, Chiocca EA, Agar NYR, Pentelute BL, Lawler SE (2017) Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents. Nat Commun 8:15623CrossRefPubMedPubMedCentral

17.

Yang ZZ, Li JQ, Wang ZZ, Dong DW, Qi XR (2014) Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 35:5226–5239CrossRefPubMed

18.

Mckinley KL, Cheeseman IM (2014) Polo-like kinase 1 licenses CENP-A deposition at centromeres. Cell 158:397–411CrossRefPubMedPubMedCentral

19.

Gao H, Zhang S, Cao S, Yang Z, Pang Z, Jiang X (2014) Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery. Mol Pharm 11:2755–2763CrossRefPubMed

20.

Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, Cho CK, Sah DWY, Stebbing D, Crosley EJ, Yaworski E (2010) Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176CrossRefPubMed

21.

Liu H, Qiao C, Yang J, Weng J, Zhang X (2014) Self-assembling doxorubicin-prodrug nanoparticles as siRNA drug delivery system for cancer treatment: in vitro and in vivo. J Mater Chem B 2:5910–5924CrossRef

22.

Shukla A, Dong K, Sharma M, Magidson V, Loncarek J (2015) Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation. Nat Commun 6:8077CrossRefPubMedPubMedCentral

23.

Zhou X, Zhan W, Bian W, Hua L, Shi Q, Xie S, Yang D, Li Y, Zhang X, Liu G (2013) GOLPH3 regulates the migration and invasion of glioma cells though RhoA. Biochem Biophys Res Commun 433:338–344CrossRefPubMed

24.

Zhang X, Ding Z, Mo J, Sang B, Shi Q, Hu J, Xie S, Zhan W, Lu D, Yang M (2015) GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1 pathway in vitro. Mol Carcinog 54:1252–1263CrossRefPubMed

25.

Abbott N, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53CrossRef

26.

Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, Jain RK (1998) Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 95:4607–4612CrossRefPubMed

27.

Miller TE, Liau BB, Wallace LC, Morton AR, Qi X, Dixit D, Factor DC, Kim LJY, Morrow JJ, Wu Q (2017) Transcription elongation factors represent in vivo cancer dependencies in glioblastoma. Nature 547:355–359CrossRefPubMedPubMedCentral

Title: Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes
Authors: Zixuan Yuan
Liang Zhao
Yafei Zhang
Shun Li
Bomin Pan
Lei Hua
Zhen Wang
Chengkun Ye
Jun Lu
Rutong Yu
Hongmei Liu
Publication date: 01-11-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-2966-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2018

Interaction of quality of life, mood and depression of patients and their informal caregivers after surgical treatment of high-grade glioma: a prospective study

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery

Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial

Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma

Postoperative stereotactic radiosurgery for patients with resected brain metastases: a volumetric analysis

Bevacizumab, irinotecan, temozolomide, tyrosine kinase inhibition, and MEK inhibition are effective against pleomorphic xanthoastrocytoma regardless of V600E status