オオサワ　シゲヒト   Oosawa Shigehito   大澤　重仁    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors
掲載誌名	正式名：Biomaterials 略　 称：Biomaterials ISSNコード：01429612/18785905
掲載区分	国外
巻・号・頁	35(20),pp.5359-5368
総ページ数	10
著者・共著者	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
発行年月	2014/07/01
概要	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