Limits...
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

a In vivo fluorescence images of A549 tumor-bearing BALB/c mice at different time points post tail-vein injection of rhodamine-labeled GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs. b Ex vivo fluorescence images of excised organs at 1.5 h post tail-vein injection
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4829570&req=5

Fig8: a In vivo fluorescence images of A549 tumor-bearing BALB/c mice at different time points post tail-vein injection of rhodamine-labeled GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs. b Ex vivo fluorescence images of excised organs at 1.5 h post tail-vein injection

Mentions: One major pitfall of in vitro studies is that they cannot be reproduced in vivo. GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs were labeled with RITC, and 2 mg/mouse was intravenously administrated into A549 tumor-bearing mice. As shown in Fig. 8, our NPs accumulated dominantly in highly perfused organs such as the liver and spleen. Moreover, the uptake of GS-PEG/HA2-Apt NPs in tumor sites was most obvious, followed by GS-PEG-Apt and GS-PEG during 90 min. This phenomenon might be due to the fact that the surface coverage of NPs altered the characteristics of their distribution in vivo [29]. Firstly, PEGylation could endow NPs a hydrophilic protective layer to repel the protein absorption, further reducing NPs elimination by the RES. Thus, the NPs possessed a good passive targeting effect. Correspondingly, three PEG-functional NPs were present in tumors at 60 and 90 min after injection. Secondly, aptamer AGRO 100 on the surface of the NPs could be recognized and bound with nucleolin-positive A549 tumor cells, later resulting in an increased level of intracellular delivery of NPs to the tumor site. Hence, modifying AGRO 100 on the NPs endows them with tumor-targeting specificity. Thus, more GS-PEG-Apt and GS-PEG/HA2-Apt were found in tumors (Fig. 8). Thirdly, HA2 peptide DNA could help NPs escape quickly from the endosome, improving the efficiency of tumor uptake.Fig. 8


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)

a In vivo fluorescence images of A549 tumor-bearing BALB/c mice at different time points post tail-vein injection of rhodamine-labeled GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs. b Ex vivo fluorescence images of excised organs at 1.5 h post tail-vein injection
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: a In vivo fluorescence images of A549 tumor-bearing BALB/c mice at different time points post tail-vein injection of rhodamine-labeled GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs. b Ex vivo fluorescence images of excised organs at 1.5 h post tail-vein injection
Mentions: One major pitfall of in vitro studies is that they cannot be reproduced in vivo. GS-PEG, GS-PEG-Apt, and GS-PEG/HA2-Apt NPs were labeled with RITC, and 2 mg/mouse was intravenously administrated into A549 tumor-bearing mice. As shown in Fig. 8, our NPs accumulated dominantly in highly perfused organs such as the liver and spleen. Moreover, the uptake of GS-PEG/HA2-Apt NPs in tumor sites was most obvious, followed by GS-PEG-Apt and GS-PEG during 90 min. This phenomenon might be due to the fact that the surface coverage of NPs altered the characteristics of their distribution in vivo [29]. Firstly, PEGylation could endow NPs a hydrophilic protective layer to repel the protein absorption, further reducing NPs elimination by the RES. Thus, the NPs possessed a good passive targeting effect. Correspondingly, three PEG-functional NPs were present in tumors at 60 and 90 min after injection. Secondly, aptamer AGRO 100 on the surface of the NPs could be recognized and bound with nucleolin-positive A549 tumor cells, later resulting in an increased level of intracellular delivery of NPs to the tumor site. Hence, modifying AGRO 100 on the NPs endows them with tumor-targeting specificity. Thus, more GS-PEG-Apt and GS-PEG/HA2-Apt were found in tumors (Fig. 8). Thirdly, HA2 peptide DNA could help NPs escape quickly from the endosome, improving the efficiency of tumor uptake.Fig. 8

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