大澤　重仁
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors
Journal Formal name：Biomaterials
Abbreviation：Biomaterials
ISSN code：01429612/18785905
Domestic / ForeginForegin
Volume, Issue, Page 35(20),pp.5359-5368
Total page number 10
Author and coauthor Anjaneyulu Dirisala, Kensuke Osada, Qixian Chen, Theofilus A Tockary, Kaori Machitani, Shigehito Osawa, Xueying Liu, Takehiko Ishii, Kanjiro Miyata, Makoto Oba, Satoshi Uchida, Keiji Itaka, Kazunori Kataoka
Publication date 2014/07/01
Summary Poly(ethylene glycol) (PEG) modification onto a gene delivery carrier for systemic application results in a trade-off between prolonged blood circulation and promoted transfection because high PEG shielding is advantageous in prolonging blood retention, while it is disadvantageous with regard to obtaining efficient transfection owing to hampered cellular uptake. To tackle this challenging issue, the present investigation focused on the structure of polyplex micelles (PMs) obtained from PEG–poly(l-lysine) (PEG–PLys) block copolymers characterized as rod-shaped structures to seek the most appreciable formulation. Comprehensive investigations conducted with particular focus on stability, PEG crowdedness, and rod length, controlled by varying PLys segment length, clarified the effect of these structural features, with particular emphasis on rod length as a critical parameter in promoting cellular uptake. PMs with rod length regulated below the critical threshold length of 200 nm fully exploited the benefits of cross-linking and the cyclic RGD ligand, consequently, exhibiting remarkable transfection efficiency comparable with that of ExGen 500 and Lipofectamine® LTX with PLUS™ even though PMs were PEG shielded. The identified PMs exhibited significant antitumor efficacy in systemic treatment of pancreatic adenocarcinoma, whereas PMs with rod length above 200 nm exhibited negligible antitumor efficacy despite a superior blood circulation property, thereby highlighting the significance of controlling the rod length of PMs to promote gene transduction.
DOI 10.1016/j.biomaterials.2014.03.037