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Emerging biotechnological strategies for non-viral antiangiogenic gene therapy

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Angiogenesis Aims and scope Submit manuscript

Abstract

Angiogenesis has emerged as a promising target of cancer treatment. With the development of biotechnology, major progress has been made in the exploring effective therapies on targeting tumor angiogenesis over the last 20 years. Gene therapy has attracted considerable interest by virtue of the capabilities of expressing sustained levels of therapeutic agents within cells of the patients. However, the major challenge of gene therapy is the efficient delivery of therapeutic gene to the target site. Compared with viral strategies, non-viral strategies were more acceptable by their widely recognized security and lower side effects. This paper reviews the basic biology of angiogenesis, the potential advantages of antiangiogenic gene therapy, the therapeutic genetic drugs developed through biotechnology, as well as the biotechnological strategies that enhancing non-viral gene therapy targeting to tumor angiogenesis in a more controlled manner, with great respect to RNA interference, ligand-directed vascular targeting strategies, vascular endothelial growth factor pathway and tumor associated macrophages targeting. In conclusion, antiangiogenic gene therapy holds great promise in advancing cancer therapy. Developing better non-viral biotechnological platforms will benefit antiangiogenic targeted cancer gene therapeutic methods, support their evaluation in human clinical trials and realize the actual utilization in the near future.

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Abbreviations

AMD:

Age-related macular degeneration

APN:

Aminopeptidase N

ASODN:

Antisense oligonucleotides

bFGF:

Basic fibroblast growth factor

bPEI:

Branched polyethylenimine

CML:

Chronic myelogenous leukemia

CNV:

Choroidal neovascularization

DAS:

Dorsal air sac

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EGFR:

Pidermal growth factor receptor

Fab:

Antibody fragment

FGF-2:

Fibroblast growth factor-2

Flk-1:

Fetal liver kinase 1

GIST:

Gastrointestinal stromal tumor

HER2:

Human epidermal growth factor receptor 2

HUVEC:

Human umbilical vein endothelial cell

IFN-γ:

Interferon-gamma

IL-12:

Interleukin-12

IV:

Intravenous injection

IVT:

Intravitreal injection

KDR:

Kinase insert domain protein receptor

LLC:

Lewis lung carcinoma

Man-SLN:

Mannan-modified SLN

mCRC:

Metastatic colorectal cancer

Mgl:

Macrophage galactose-type lectin

MMPs:

Matrixmetalloproteinases

mRNA:

Messenger RNA

MVD:

Microvessel density

NCI:

National Cancer Institute

NGR:

Asparagine-glycine-arginine

NK:

Natural killer

NSCLC:

Non-small cell lung cancer

PAA:

Poly(amido amine)

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

pDMAEMA:

Poly(2-(dimethyl-amino) ethylmethacrylate)

PEC:

Polyelectrolyte complex

PEDF:

Pigment epithelium-derived factor

PEI:

Poly(ethyleneimine)

PGF:

Placenta growth factor

Ph + ALL:

Philadelphia chromosome-positive acute lymphoblastic leukemia

PIGF:

Placenta growth factors

PLGA:

Poly(lactic-co-glycolic acid)

PLL:

Poly(l-lysine)

PVDF:

Poly(vinylidene fluoride)

RCC:

Renal cell carcinoma

RGD:

Arginine-glycine-aspartic acid

RNAi:

RNA interference

RPE:

Retinal pigment epithelial

RTK:

Receptor tyrosine kinase

RTKIs:

Receptor tyrosine kinase inhibitors

sFlt-1:

Soluble vascular endothelial growth factor receptor-1

siRNA:

Small interfering RNA

SLN:

Solid lipid nanoparticles

TAM:

Tumor associated macrophages

THSBs:

Thrombospondins

TNF-α:

Tumor necrosis factor-alpha

VEGF:

Vascular endothelial growth factor

VEGFR-2:

Vascular endothelial growth factor receptor-2

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Acknowledgments

This work was supported by the National Natural Science Foundation (No. 81072585), the Shandong Province Natural Science Foundation (No. ZR2009CM011), the Graduate Independent Innovation Foundation of Shandong University (No. 21310070613252).

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The authors have no potential conflicts of interest to disclose.

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    Chunxi Liu & Na Zhang

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Liu, C., Zhang, N. Emerging biotechnological strategies for non-viral antiangiogenic gene therapy. Angiogenesis 15, 521–542 (2012). https://doi.org/10.1007/s10456-012-9295-8

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