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In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery.

Zhao X, Wang J, Tao S, Ye T, Kong X, Ren L - Nanoscale Res Lett (2016)

Bottom Line: The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively.More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection.Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China. zhaoxueqin2004@163.com.

ABSTRACT
The non-viral gene delivery system is an attractive alternative to cancer therapy. The clinical success of non-viral gene delivery is hampered by transfection efficiency and tumor targeting, which can be individually overcome by addition of functional modules such as cell penetration or targeting. Here, we first engineered the multifunctional gelatin/silica (GS) nanovectors with separately controllable modules, including tumor-targeting aptamer AGRO100, membrane-destabilizing peptide HA2, and polyethylene glycol (PEG), and then studied their bio-distribution and in vivo transfection efficiencies by contrast resonance imaging (CRI). The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively. Functional GS-PEG nanoparticles mainly accumulated in the liver and tumor, with the lowest uptake by the heart and brain. Moreover, the synergistic effects of tumor-targeting aptamer AGRO100 and fusogenic peptide HA2 promoted the efficient cellular internalization in the tumor site. More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection. Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

No MeSH data available.


Related in: MedlinePlus

Hydrodynamic size changes of the GS coated with PEG, aptamer, and HA2 peptide incubated in PBS plus 10 % FBS at 37 °C for 24 h
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Fig4: Hydrodynamic size changes of the GS coated with PEG, aptamer, and HA2 peptide incubated in PBS plus 10 % FBS at 37 °C for 24 h

Mentions: The net surface charge of the nanoparticles also plays a critical role in the clearance of the nanoparticles from the animal body due to different adsorption effects on physiological lipoproteins in the systemic circulation [26]. Hence, we simply mimicked the body environment by adding FBS in the culture medium to evaluate the strength of the nanovectors in the biological environment. As showed in Fig. 4, naked GS size increased by 12.5 %, while PEG-modified nanoparticles increased by less than 5 %, exhibiting long serum stability. The presence of PEG may increase the nanoparticle’s colloidal stability through steric hindrance and provide non-fouling properties [27].Fig. 4


In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery.

Zhao X, Wang J, Tao S, Ye T, Kong X, Ren L - Nanoscale Res Lett (2016)

Hydrodynamic size changes of the GS coated with PEG, aptamer, and HA2 peptide incubated in PBS plus 10 % FBS at 37 °C for 24 h
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829570&req=5

Fig4: Hydrodynamic size changes of the GS coated with PEG, aptamer, and HA2 peptide incubated in PBS plus 10 % FBS at 37 °C for 24 h
Mentions: The net surface charge of the nanoparticles also plays a critical role in the clearance of the nanoparticles from the animal body due to different adsorption effects on physiological lipoproteins in the systemic circulation [26]. Hence, we simply mimicked the body environment by adding FBS in the culture medium to evaluate the strength of the nanovectors in the biological environment. As showed in Fig. 4, naked GS size increased by 12.5 %, while PEG-modified nanoparticles increased by less than 5 %, exhibiting long serum stability. The presence of PEG may increase the nanoparticle’s colloidal stability through steric hindrance and provide non-fouling properties [27].Fig. 4

Bottom Line: The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively.More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection.Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China. zhaoxueqin2004@163.com.

ABSTRACT
The non-viral gene delivery system is an attractive alternative to cancer therapy. The clinical success of non-viral gene delivery is hampered by transfection efficiency and tumor targeting, which can be individually overcome by addition of functional modules such as cell penetration or targeting. Here, we first engineered the multifunctional gelatin/silica (GS) nanovectors with separately controllable modules, including tumor-targeting aptamer AGRO100, membrane-destabilizing peptide HA2, and polyethylene glycol (PEG), and then studied their bio-distribution and in vivo transfection efficiencies by contrast resonance imaging (CRI). The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively. Functional GS-PEG nanoparticles mainly accumulated in the liver and tumor, with the lowest uptake by the heart and brain. Moreover, the synergistic effects of tumor-targeting aptamer AGRO100 and fusogenic peptide HA2 promoted the efficient cellular internalization in the tumor site. More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection. Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

No MeSH data available.


Related in: MedlinePlus