Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier

For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. Th...

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Main Authors: Ryoma Teranishi, Ryota Matsuki, Eiji Yuba, Atsushi Harada, Kenji Kono
Format: Article
Language:English
Published: MDPI AG 2016-12-01
Series:Pharmaceutics
Subjects:
Online Access:http://www.mdpi.com/1999-4923/9/1/4
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author Ryoma Teranishi
Ryota Matsuki
Eiji Yuba
Atsushi Harada
Kenji Kono
author_facet Ryoma Teranishi
Ryota Matsuki
Eiji Yuba
Atsushi Harada
Kenji Kono
author_sort Ryoma Teranishi
collection DOAJ
description For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells.
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spelling doaj.art-fc4527d6281b466b8460eb36edb6e2b22022-12-22T02:14:36ZengMDPI AGPharmaceutics1999-49232016-12-0191410.3390/pharmaceutics9010004pharmaceutics9010004Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic BarrierRyoma Teranishi0Ryota Matsuki1Eiji Yuba2Atsushi Harada3Kenji Kono4Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, JapanFor the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells.http://www.mdpi.com/1999-4923/9/1/4hollow nanocapsulesdoxorubicindual responsiveelectrostatic barrierdrug delivery systemself-assembled polymers
spellingShingle Ryoma Teranishi
Ryota Matsuki
Eiji Yuba
Atsushi Harada
Kenji Kono
Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
Pharmaceutics
hollow nanocapsules
doxorubicin
dual responsive
electrostatic barrier
drug delivery system
self-assembled polymers
title Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
title_full Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
title_fullStr Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
title_full_unstemmed Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
title_short Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
title_sort doxorubicin delivery using ph and redox dual responsive hollow nanocapsules with a cationic electrostatic barrier
topic hollow nanocapsules
doxorubicin
dual responsive
electrostatic barrier
drug delivery system
self-assembled polymers
url http://www.mdpi.com/1999-4923/9/1/4
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