Vorinostat-Polymer Conjugate Nanoparticles for Acid-Responsive Delivery and Passive Tumor Targeting

被引：26

作者：

Denis, Iza ^{[1
,2
,3
]}

el Bahhaj, Fatima ^{[5
]}

Collette, Floraine ^{[4
]}

Delatouche, Regis ^{[5
]}

Gueugnon, Fabien ^{[1
,2
,3
]}

Pouliquen, Daniel ^{[1
,2
,3
]}

Pichavant, Loic ^{[4
]}

Heroguez, Valerie ^{[4
]}

Gregoire, Marc ^{[1
,2
,3
]}

Bertrand, Philippe ^{[5
,6
]}

Blanquart, Christophe ^{[1
,2
,3
,6
]}

机构：

[1] INSERM, UMR 892, F-44000 Nantes, France

[2] CNRS, UMR 6299, F-44000 Nantes, France

[3] Univ Nantes, F-44007 Nantes 1, France

[4] CNRS, Lab Chim Polymeres Organ, UMR 5629, F-33607 Pessac, France

[5] CNRS, Inst Chim Milieux & Mat Poitiers, UMR 7582, F-86000 Poitiers, France

[6] Reseau Epigenet Canc Pole Grand Ouest, Grand Ouest, France

来源：

BIOMACROMOLECULES | 2014年 / 15卷 / 12期

关键词：

HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; IN-VIVO; MESOTHELIOMA; GROWTH; CELLS; SERUM; NANOCARRIERS; METABOLITES; APOPTOSIS;

D O I：

10.1021/bm501338r

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In vivo histone deacetylase (HDAC) inhibition by vorinostat under clinically acceptable dosing is limited by its poor pharmacokinetics properties. A new type of nontoxic pH-responsive delivery system has been synthesized by ring-opening metathesis polymerization, allowing for the selective distribution of vorinostat in mesothelioma tumors in vivo and subsequent histone reacetylation. The delivery system is synthesized by generic click chemistry, possesses native stealth properties for passive tumor targeting, and does not need additional chemistry for cellular internalization. Although vorinostat alone at 50 mg/kg in mice showed no effect, our new delivery system with 2 mg/kg vorinostat promoted histone reacetylation in tumors without side effects, demonstrating that our strategy improves the activity of this HDAC inihibitor in vivo.

引用

页码：4534 / 4543

页数：10

共 25 条

[1] Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression [J].