Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of Biocompatible Small Plasmid Complex Particles Consisting of pDNA, Anionic Polysaccharide, and Fully Deprotected Linear Polyethylenimine

Pharmaceutics

Yoshiyuki Koyama³  Kikuya Sugiura²  Chieko Yoshihara¹  Toshio Inaba²  Tomoko Ito³ 

[1] Department of Home Economics, Otsuma Women’s University, 12 Sanbancho, Chiyoda-ku, Tokyo 102-8357, Japan; E-Mail:;Graduate School of Life and Environmental Sciences, Osaka Prefecture University 1-58 Rinku-oraikita, Izumisano, Osaka 598-8531, Japan; E-Mails:;Japan Anti-tuberculosis Association, Shin-Yamanote Hospital, 3-6-1 Suwa-cho, Higashimurayama, Tokyo 189-0021, Japan; E-Mail:

关键词: non-viral;    transfection;    plasmid;    Polyethylenimine “Max”;    freeze-drying;    hyaluronic acid;    chondroitin sulfate;    antitumor;    cytokine;    nanoparticle;   

DOI  :  10.3390/pharmaceutics7030152

来源: mdpi

【 摘 要 】

We have reported that ternary complexes of plasmid DNA with conventional linear polyethylenimine (l-PEI) and certain polyanions were very stably dispersed, and, with no cryoprotectant, they could be freeze-dried and re-hydrated without the loss of transfection ability. These properties enabled the preparation of a concentrated suspension of very small pDNA complex, by preparing the complexes at highly diluted conditions, followed by condensation via lyophilization-and-rehydration procedure. Recently, a high potency linear polyethylenimine having no residual protective groups, i.e., Polyethylenimine “Max” (PEI “Max”), is available, which has been reported to induce much higher gene expression than conventional l-PEI. We tried to prepare the small DNA/PEI “Max”/polyanion complexes by a similar freeze-drying method. Small complex particles could be obtained without apparent aggregation, but transfection activity of the rehydrated complexes was severely reduced. Complex-preparation conditions were investigated in details to achieve the freeze-dried DNA/PEI “Max”/polyanion small ternary complexes with high transfection efficiency. DNA/PEI “Max”/polyanion complexes containing cytokine-coding plasmids were then prepared, and their anti-tumor therapeutic efficacy was examined in tumor-bearing mice.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.