Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors

被引：68

作者：

Dirisala, Anjaneyulu ^{[1
]}

Osada, Kensuke ^{[1
,5
]}

Chen, Qixian ^{[2
]}

Tockary, Theofilus A. ^{[2
]}

Machitani, Kaori ^{[2
]}

Osawa, Shigehito ^{[2
]}

Liu, Xueying ^{[3
]}

Ishii, Takehiko ^{[1
]}

Miyata, Kanjiro ^{[3
]}

Oba, Makoto ^{[4
]}

Uchida, Satoshi ^{[3
]}

Itaka, Keiji ^{[3
]}

Kataoka, Kazunori ^{[1
,2
,3
]}

机构：

[1] Univ Tokyo, Grad Sch Engn, Dept Bioengn, Bunkyo Ku, Tokyo 1138656, Japan

[2] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, Tokyo 1138656, Japan

[3] Univ Tokyo, Grad Sch Med, Div Clin Biotechnol, Ctr Dis Biol & Integrat Med,Bunkyo Ku, Tokyo 1130033, Japan

[4] Nagasaki Univ, Sch Pharmaceut Sci, Div Pharmaceut Chem, Dept Mol Med Sci, Nagasaki 8528521, Japan

[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan

来源：

BIOMATERIALS | 2014年 / 35卷 / 20期

基金：

日本学术振兴会;

关键词：

DNA; Micelle; Nanoparticle; Gene transfer; In vitro test; In vivo test; CYCLIC RGD PEPTIDE; GLYCOL)-POLY(L-LYSINE) BLOCK-COPOLYMER; HEPARAN-SULFATE PROTEOGLYCANS; PLASMID DNA; GROWTH-FACTOR; INTRACELLULAR TRAFFICKING; MEDIATED ENDOCYTOSIS; VASCULAR-LESIONS; DISULFIDE BOND; DRUG-DELIVERY;

D O I：

10.1016/j.biomaterials.2014.03.037

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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 (R) LTX with PLUS (TM) 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. (c) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5359 / 5368

页数：10

共 55 条

[1] Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation [J].

Akagi, D. ;

Oba, M. ;

Koyama, H. ;

Nishiyama, N. ;

Fukushima, S. ;

Miyata, T. ;

Nagawa, H. ;

Kataoka, K. .

GENE THERAPY, 2007, 14 (13) :1029-1038

[2] Functions of cell surface heparan sulfate proteoglycans [J].

Bernfield, M ;

Götte, M ;

Park, PW ;

Reizes, O ;

Fitzgerald, ML ;

Lincecum, J ;

Zako, M .

ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :729-777

[3] A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].

BOUSSIF, O ;

LEZOUALCH, F ;

ZANTA, MA ;

MERGNY, MD ;

SCHERMAN, D ;

DEMENEIX, B ;

BEHR, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301

[4] Extracellular barriers to in Vivo PEI and PEGylated PEI polyplex-mediated gene delivery to the liver [J].

Burke, Rob S. ;

Pun, Suzie H. .

BIOCONJUGATE CHEMISTRY, 2008, 19 (03) :693-704

[5] Supramolecular Nanodevices: From Design Validation to Theranostic Nanomedicine [J].

Cabral, Horacio ;

Nishiyama, Nobuhiro ;

Kataoka, Kazunori .

ACCOUNTS OF CHEMICAL RESEARCH, 2011, 44 (10) :999-1008

[6] Regulated portals of entry into the cell [J].

Conner, SD ;

Schmid, SL .

NATURE, 2003, 422 (6927) :37-44

[7] THE PREPARATION OF N-CARBOXYANHYDRIDES OF ALPHA-AMINO-ACIDS USING BIS(TRICHLOROMETHYL)CARBONATE [J].

DALY, WH ;

POCHE, D .

TETRAHEDRON LETTERS, 1988, 29 (46) :5859-5862

[8]

Erdreich-Epstein A, 2000, CANCER RES, V60, P712

[9] Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors [J].

Ge, Zhishen ;

Chen, Qixian ;

Osada, Kensuke ;

Liu, Xueying ;

Tockary, Theofilus A. ;

Uchida, Satoshi ;

Dirisala, Anjaneyulu ;

Ishii, Takehiko ;

Nomoto, Takahiro ;

Toh, Kazuko ;

Matsumoto, Yu ;

Oba, Makoto ;

Kano, Mitsunobu R. ;

Itaka, Keiji ;

Kataoka, Kazunori .

BIOMATERIALS, 2014, 35 (10) :3416-3426

[10] Shape effects of filaments versus spherical particles in flow and drug delivery [J].

Geng, Yan ;

Dalhaimer, Paul ;

Cai, Shenshen ;

Tsai, Richard ;

Tewari, Manorama ;

Minko, Tamara ;

Discher, Dennis E. .

NATURE NANOTECHNOLOGY, 2007, 2 (04) :249-255

← 1 2 3 4 5 6 →