Construction of α-Cyclodextrin-Based Stimuli-Responsive Gene Delivery Nanovectors: In Vitro, Ex Vivo, and In Vivo Investigations
| Autor: | Yi-Yang Jia, Wei He, Xi-Xi Ma, Li-Zhong Hu, Yuan-Tao Ma, Zhou Siyuan, Ning Wan, Ya-Xuan Zhang, Zhang Bangle |
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| Rok vydání: | 2019 |
| Předmět: |
Chemistry
Endosome 0206 medical engineering Endocytic cycle Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering 02 engineering and technology Transfection Gene delivery 021001 nanoscience & nanotechnology 020601 biomedical engineering Controlled release In vitro Cell biology In vivo General Materials Science 0210 nano-technology Ex vivo |
| Zdroj: | Journal of Biomedical Nanotechnology. 15:1654-1672 |
| ISSN: | 1550-7033 |
| DOI: | 10.1166/jbn.2019.2799 |
| Popis: | Stimuli-responsive materials are promising paradigm applied to construct diagnostic and therapeutic intracellular controlled release vectors, while highlighting many challenges and opportunities. In this paper, six α-cyclodextrin-based supramolecular nanovectors were constructed and the efficacy of amine groups, stimuli-responsive profiles and endocytic mechanisms were investigated. The results indicated that the designed supermolecules can compact DNA to form stable complexes and display low cytotoxicity. Among them, PRPEI-2 with suitable PEI amine group exhibited enhanced transfecting performance, high dilution stability, nice serum compatibility, and good acid-responsive profiles to enable endosome escape, significantly higher than commercially available transfecting agent PEI25000, the most effective vector studied to date. The endocytic uptake mechanisms involved in the transfection was mainly through clathrin-mediated pathway, which is closely associated with and can be improved by endosome escape. Moreover, PRPEI-2/DNA polyplex can be effectively expressed in vivo even after 48 h via only single tail-vein injection, and the gene expression and main tissue distribution appeared in the testis, liver, brain and spleen. These excellent characteristics demonstrated that the supramolecular PRPEI-2 represents an excellent prospect as stimuli-responsive nanovectors for gene diagnosis and therapy. |
| Databáze: | OpenAIRE |
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