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Title 

Dual pH-sensitive oxidative stress generating micellar nanoparticles as a novel anticancer therapeutic agent

Authors 

S ParkB KwonW YangE HanW YooByoung-Mog KwonD Lee

Publisher 

Elsevier

Issue Date 

2014

Citation 

Journal of Controlled Release, vol. 196, no. 0, pp. 19-27

Keywords 

ApoptosisCancerMicellesOxidative stressReactive oxygen species

Abstract 

Cancer cells are under oxidative stress due to a large production of reactive oxygen species (ROS), which involve in cell proliferation and cancer promotion and progression. On the other hand, ROS promotes cell death, depending on the rate of ROS production and the activity of antioxidant systems. Recently, "oxidation therapy" has arisen as a promising anticancer strategy, which can be achieved by inducing the generation of cytotoxic level of ROS or inhibiting the antioxidant systems in tumor cells. Here, we report oxidative stress amplifying nanoplatforms as novel anticancer therapeutics, which are able not only to suppress antioxidant but also to generate ROS simultaneously in acidic tumor microenvironments. The oxidative stress amplifying nanoplatforms are composed of dual pH-sensitive PBCAE copolymer, polymeric prodrug of BCA (benzoyloxycinnamaldehyde) and heme oxygenase-1 (HO-1) inhibiting zinc protoporphyrin (ZnPP). PBCAE was designed to incorporate ROS-generating BCA in its backbone via acid-cleavable acetal linkages and self-assemble to form micelles that encapsulate ZnPP. In vitro proof-of-concept studies revealed that ZnPP encapsulated in PBCAE micelles suppressed HO-1 to make cancer cells more vulnerable to BCA-induced ROS, leading to enhanced apoptotic cell death. In addition, ZnPP-loaded PBCAE micelles significantly suppressed the tumor growth in human cancer xenograft mouse models. We believe that oxidative stress amplifying micellar nanoparticles have a great potential as novel redox anticancer therapeutics.

ISSN 

0168-3659

Link 

http://dx.doi.org/10.1016/j.jconrel.2014.09.017

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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