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Table 1 Classification of electrospun nanofiber-mediated gene delivery approaches

From: Electrospun nanofibers as versatile interfaces for efficient gene delivery

Vector loading methods

Vectors

Genes

Target cells

Results

Ref

Vector encapsulation

Virus (Ad)

GFP, RFP

HEK293T

• Sustained and controlled viral release for 30 days.

[30]

• Localized gene expression from electrospun scaffolds.

Plasmid DNA

β-Gal, GFP

MC3T3-E1

• Gene expression by the released DNA 48 h after seeding

[47]

• Burst release of majority of encapsulated plasmid DNA within 30 minutes.

Cdk2i, EGFPi

MCF-7 cell

• Sustained release over 21 days

[115]

• ~40% decrease in proliferation of breast cancer cells compared with control scaffold

EGFP

Rat fibroblasts

• Extended release of pDNA and transgene expression over 60 days.

[55]

Virus (AAV)

GFP

NIH3T3

• Sustained viral release for 7 days.

[48]

• Maintained transgene expression (>90%) on the scaffolds for 7 days.

Plasmid DNA/chitosan nanoparticle

BMP-2

hMSC

• Sustained release for 45 ~ 55 days

[56]

• DNA/chitosan nanoparticles encapsulated electrospun scaffolds as a favorable DNA delivery device with regard to cell transfection efficiency and cell viability

Plasmid DNA/LEL polyplex

β-Gal, GFP

MC3T3

• Transgene expression on DNA-incorporating electrospun scaffolds 24 h after seeding.

[57, 80]

• Sustained release for 7 days.

siRNA/CPP polyplex

Col1A1 silencing

Human dermal fibroblasts, in vivo

• Prolonged in vitro gene silencing duration by 2 ~ 3-fold.

[58]

• In vivo gene silencing for 4 weeks.

Plasmid DNA/PEI

EGFP

NIH3T3

• Controlled release time from 6 days to 25 days by internal structures and porogens.

[64]

• 10-fold increased gene expression on the scaffolds compared to simple pDNA/PELA blends.

VEGF/eGFP & bFGF/eGFP

HUVEC

• Sustained release for 4 weeks

[65]

• Significantly higher vessel densities

bFGF/GFP

BEF, in vivo

• Sustained release for 26 days

[84]

• 4 ~ 6-fold increased bFGF expression compared with post-electrospinning delivery after 7 day incubation

• Significantly higher wound recovery rate compared with post-electrospinning delivery

siRNA/chitosan polyplex

EGFP silencing

EGFP expressing human lung carcinoma cell lines

• Sustained and controlled delivery for 30 days.

[67]

• Prolonged in vitro gene silencing duration by 3 ~ 4-fold compared to the bolus delivery.

siRNA

GAPDH silencing

HEK293, NIH3T3

• Sustained release of siRNA for 28 days.

[68]

• Gene silencing on scaffolds in presence of additional transfection agents.

• Enhanced gene silencing capability with additional transfection agents in the media.

siRNA/transfect-ion reagent complex

GAPDH silencing

NIH3T3

• Sustained release of siRNA and gene silencing on the scaffolds for at least 28 days.

[69]

• Improved gene silencing capability with transfection agents supplemented in the media.

Solid-in-oil dispersion of plasmid DNA

Luciferase

N/A

• Release profile controlled by degrading rates of fibers.

[81]

• 10-fold increases in functional integrity of released pDNA compared to mixed mesh.

Plasmid DNA/calcium phosphate nanoparticle

VEGF/eGFP & bFGF/eGFP

HUVEC, hAoSMC

• Sustained release for 4 weeks

[83]

• Significantly higher densities of blood vessels and mature vessels

Vector immobilization

Virus (AAV)

GFP, Luciferase

HEK293T

• Three-dimensional and uniaxially aligned transgene expression

[33]

• 4-fold enhanced transgene expression levels compared to 2D electrospun scaffolds.

Plasmid DNA

EGFP

Glioblastoma cells

• Transgene expression by the released DNA from the fibers (maximum transfection efficiency > 90%).

[45]

Luciferase

COS-7

• Retained gene expression on the fibers for 5 days after seeding.

[46]

• 2-fold increased gene delivery efficiency of electrospun fibers over that of flat films.

GFP, Dsred

HEK293, MSC, in vivo

• 10-fold increase in gene expression intensity compared to PCL fibers in vivo.

[59]

EGFP-N1

NIH3T3, in vivo

• MMP-2 responsive release of DNA

[66]

• Significantly enhanced gene expression in wound tissue compared to naked DNA delivery

Luciferase, KGF

NIH3T3, in vivo

• Sustained expression for 7 days

[76]

• 65% smaller epithelial gap in KGF scaffold treated wounds than in untreated wounds

hEGF

HDF, in vivo

• MMP-2 responsive release of DNA

[85]

• Approximately 2-fold increased wound closure compared with non-treated wounds

EGFP

MC3T3-E1

• Controlled gradients of pDNA concentration and gene expression level by spatially regulating rates of chemical reactions.

[98]

Virus (AAV)

GFP

HEK293T

• Patterned and localized gene vectors and gene expression on the scaffolds.

[60]

• 2-fold increase in transfection efficiency compared with unmodified virus delivery.

Plasmid DNA/liposome

RUNX2/eGFP

hBMSC

• Long-term gene expression for 21 days

[77]

• Improved osteogenic differentiation of stem cells

siRNA/PEI polyplexes & siRNA/ transfection reagent complex

TSP-2 silencing

hAoSMC

• Down-regulated TSP-2 mRNA expression

[78]

Plasmid DNA/chitosan nanoparticle

BMP-2

in vivo

• Different bone healing performance depending on the loading methods

[82]

• Improved bone healing for DNA/chitosan nanoparticles adsorbed electrospun scaffolds at 4 weeks of treatment

siRNA

MMP-2 silencing

HDF, in vivo

• MMP-2 responsive release of DNA

[86]

• Faster wound recovery rate compared with siRNA solution delivery

Plasmid DNA/ssPEI

Luciferase, RFP, VEGF

H9C2 myoblastic cell

• Enhanced transfection efficiency compared to bolus delivery

[87]

• Successful expression of the VEGF gene in the cells

 

siRNA/ transfection reagent complex

REST silencing

NPC

• Enhanced neural marker expression and neuronal differentiation

[88]