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Abstract
Background
Nanobiotechnology can provide more efficient tools for diagnosis, targeted and personalized therapy, and increase the chances of brain tumor treatment being successful. Use of nanoparticles is a promising strategy for overcoming the blood–brain barrier and delivering drugs to the brain. Gelatin-siloxane (GS) nanoparticles modified with Tat peptide can enhance plasmid DNA transfection efficiency compared with a commercial reagent.
Methods
SynB-PEG-GS nanoparticles are membrane-penetrable, and can cross the blood–brain barrier and deliver a drug to its target site in the brain. The efficiency of delivery was investigated in vivo and in vitro using brain capillary endothelial cells, a cocultured blood–brain barrier model, and a normal mouse model.
Results
Our study demonstrated that both SynB-PEG-GS and PEG-GS nanoparticles had a spherical shape and an average diameter of 150–200 nm. It was shown by MTT assay that SynB-PEG-GS nanoparticles had good biocompatibility with brain capillary endothelial cells. Cellular uptake by SynB-PEG-GS nanoparticles was higher than that for PEG-GS nanoparticles for all incubation periods. The amount of SynB-PEG-GS nanoparticles crossing the cocultured blood–brain barrier model was significantly higher than that of PEG-GS nanoparticles at all time points measured (P < 0.05). In animal testing, SynB-PEG-GS nanoparticle levels in the brain were significantly higher than those of PEG-GS nanoparticles at all time points measured (P < 0.01). In contrast with localization in the brain, PEG-GS nanoparticle levels were significantly higher than those of SynB-PEG-GS nanoparticles (P < 0.01) in the liver.
Conclusion
This study indicates that SynB-PEG-GS nanoparticles have favorable properties with regard to morphology, size distribution, and toxicity. Moreover, the SynB-PEG-GS nanoparticles exhibited more efficient brain capillary endothelial cell uptake and improved crossing of the blood–brain barrier. Further, biodistribution studies of rhodamine-loaded nanoparticles demonstrated that modification with the SynB peptide could not only improve the ability of PEG-GS nanoparticles to evade capture in the reticuloendothelial system but also enhance their efficiency in crossing the blood–brain barrier.
Acknowledgment
This work was financially supported by the National Natural Science Foundation of China (81172394), the National Natural Science Foundation of China (30970733), the National Basic Research Program of China (2010CB732402), and the Natural Science Foundation of Fujian Province of China (2006J0188).
Disclosure
The authors report no conflicts of interest in this work.