A Biocompatible Oxidation-Triggered Carrier Polymer with Potential in Therapeutics

被引：343

作者：

Broaders, Kyle E. ^{[1
]}

Grandhe, Sirisha ^{[1
]}

Frechet, Jean M. J. ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2011年 / 133卷 / 04期

关键词：

HYDROGEN-PEROXIDE; DRUG-RELEASE; DEXTRAN; MICROSPHERES; ACTIVATION; EXPRESSION; STRATEGY; BIOLOGY; CELLS;

D O I：

10.1021/ja110468v

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of greater than 1 week in the absence of H2O2. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8(+) T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA. Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.

引用

页码：756 / 758

页数：3

共 25 条

[1] Acetal-derivatized dextran:: An acid-responsive biodegradable material for therapeutic applications [J].

Bachelder, Eric M. ;

Beaudette, Tristan T. ;

Broaders, Kyle E. ;

Dashe, Jesse ;

Frechet, Jean M. J. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (32) :10494-+

[2] In Vivo Studies on the Effect of Co-Encapsulation of CpG DNA and Antigen in Acid-Degradable Microparticle Vaccines [J].

Beaudette, Tristan T. ;

Bachelder, Eric M. ;

Cohen, Joel A. ;

Obermeyer, Allie C. ;

Broaders, Kyle E. ;

Frechet, Jean M. J. ;

Kang, Eun-Suk ;

Mende, Ines ;

Tseng, William W. ;

Davidson, Matthew G. ;

Engleman, Edgar G. .

MOLECULAR PHARMACEUTICS, 2009, 6 (04) :1160-1169

[3] Sonication parameters for the preparation of biodegradable nanocapsules of controlled size by the double emulsion method [J].

Bilati, U ;

Allémann, E ;

Doelker, E .

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 2003, 8 (01) :1-9

[4] Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy [J].

Broaders, Kyle E. ;

Cohen, Joel A. ;

Beaudette, Tristan T. ;

Bachelder, Eric M. ;

Frechet, Jean M. J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (14) :5497-5502

[5] A selective, cell-permeable optical probe for hydrogen peroxide in living cells [J].

Chang, MCY ;

Pralle, A ;

Isacoff, EY ;

Chang, CJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (47) :15392-15393

[6] Acetal-Modified Dextran Microparticles with Controlled Degradation Kinetics and Surface Functionality for Gene Delivery in Phagocytic and Non-Phagocytic Cells [J].

Cohen, Joel A. ;

Beaudette, Tristan T. ;

Cohen, Jessica L. ;

Brooders, Kyle E. ;

Bachelder, Eric M. ;

Frechet, Jean M. J. .

ADVANCED MATERIALS, 2010, 22 (32) :3593-+

[7]

Egilmez NK, 2000, CANCER RES, V60, P3832

[8] Synthesis and In Vivo Antitumor Efficacy of PEGylated Poly(L-lysine) Dendrimer-Camptothecin Conjugates [J].

Fox, Megan E. ;

Guillaudeu, Steve ;

Frechet, Jean M. J. ;

Jerger, Katherine ;

Macaraeg, Nichole ;

Szoka, Francis C. .

MOLECULAR PHARMACEUTICS, 2009, 6 (05) :1562-1572

[9]

Gopin A., 2001, ANGEW CHEM INT EDIT, V42, P327

[10] CONTROLLED DRUG RELEASE FROM POLY(ORTHO ESTERS) [J].

HELLER, J .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1985, 446 :51-66

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