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Authors Wang F, Pang J, Huang L, Wang R, Li D, Sun K, Wang L, Zhang L
Received 30 July 2017
Accepted for publication 7 December 2017
Published 8 February 2018 Volume 2018:13 Pages 857—875
DOI https://doi.org/10.2147/IJN.S147747
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
Background: Nanomedicine, which is the application of nanotechnology in
medicine to make medical diagnosis and treatment more accurate, has great
potential for precision medicine. Despite some improvements in nanomedicine,
the lack of efficient and low-toxic vectors remains a major obstacle.
Objective: The aim of this study was to prepare an
efficient and low-toxic vector which could deliver astrocyte elevated gene-1 (AEG-1 ) small interfering RNA
(siRNA; siAEG-1) into osteosarcoma cells effectively and silence the targeted
gene both in vitro and in vivo.
Materials and methods: We prepared a novel polysaccharide derivative by
click conjugation of azidized chitosan with propargyl focal point poly
(L-lysine) dendrons (PLLD) and subsequent coupling with folic acid (FA;
Cs-g-PLLD-FA). We confirmed the complexation of siAEG-1and Cs-g-PLLD or
Cs-g-PLLD-FA by gel retardation assay. We examined the cell cytotoxicity, cell
uptake, cell proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in
osteosarcoma cells. In osteosarcoma 143B cells tumor-bearing mice models, we
established the therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1.
Results: Cs-g-PLLD-FA could completely encapsulate
siAEG-1 and showed low cytotoxicity in osteosarcoma cells and tumour-bearing
mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were capable of transferring
siAEG-1 into osteosarcoma cells efficiently, and the knockdown of AEG-1
resulted in the inhibition of tumour cell proliferation and invasion. In
addition, caudal vein injecting of Cs-g-PLLD-FA/siAEG-1 complexes inhibited
tumor growth and lung metastasis in tumor-bearing mice by silencing AEG-1 and
regulating MMP-2/9.
Conclusion: In summary, Cs-g-PLLD-FA nanoparticles are a
promising system for the effective delivery of AEG-1 siRNA for treating
osteosarcoma.
Keywords: chitosan, gene
delivery, astrocyte elevated gene-1 , small
interfering RNA, osteosarcoma