title: In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery.
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.
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China. zhaoxueqin2004@163.com.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: SiJie
authors.initials: S
authors.lastname: Tao
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, People's Republic of China. renlei@xmu.edu.cn.|Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen University, Xiamen, 361005, People's Republic of China. renlei@xmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
keywords: Cellular uptake and transfection; In vivo and ex vivo imaging; In vivo transfection; Non-viral vector; Surface modification