posted on 2017-08-11, 00:00authored byWei Yin, Junjie Li, Wendong Ke, Zengshi Zha, Zhishen Ge
The
improved antioxidant system
of cancer cells renders them well-adaptive to the intrinsic oxidative
stress in tumor tissues. On the other hand, cancer cells are more
sensitive to elevated tumor oxidative stress as compared with normal
cells due to their deficient reactive oxygen species-eliminating systems.
Oxidation therapy of cancers refers to the strategy of killing cancer
cells through selectively increasing the oxidative stress in tumor
tissues. In this article, to amplify the oxidation therapy, we develop
integrated nanoparticles with the properties to elevate tumor oxidative
stress and concurrently suppress the antioxidative capability of cancer
cells. The amphiphilic block copolymer micelles of poly(ethylene glycol)-b-poly[2-((((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)carbonyl)oxy)ethyl
methacrylate] (PEG-b-PBEMA) are integrated with palmitoyl
ascorbate (PA) to form hybrid micelles (PA-Micelle). PA molecules
at pharmacologic concentrations serve as a prooxidant to upregulate
the hydrogen peroxide (H2O2) level in tumor
sites and the PBEMA segment exhibits H2O2-triggered
release of quinone methide for glutathione depletion to suppress the
antioxidative capability of cancer cells, which synergistically and
selectively kill cancer cells for tumor growth suppression. Given
the significantly low side toxicity against normal tissues, this novel
integrated nanoparticle design represents a novel class of nanomedicine
systems for high-efficiency oxidation therapy with the potentials
to be translated to clinical applications.