Abstract
Cancer hallmarks allow the complexity and heterogeneity of tumor biology to be better understood, leading to the discovery of various promising targets for cancer therapy. An amorphous iron oxide nanoparticle (NP)-based RNAi strategy is developed to co-target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton-like reaction. This strategy has the following features for systemic siRNA delivery: 1) siRNA encapsulation within NPs for improving systemic stability; 2) effective endosomal escape through osmotic pressure and/or endosomal membrane oxidation; 3) small size for enhancing tumor tissue penetration; and 4) triple functions (RNAi, Fenton-like reaction, and MRI) for combinatorial therapy and in vivo tracking.
Keywords:
MRI; RNAi; cancer hallmarks; iron oxide nanoparticles; tumor penetration.
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Endosomes / chemistry
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Endosomes / metabolism
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Ferric Compounds / chemistry
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Humans
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Hydrogen Peroxide / chemistry
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Hydrogen Peroxide / pharmacology
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Hydrogen Peroxide / therapeutic use
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Hydroxyl Radical / metabolism
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Iron / chemistry
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Iron / pharmacology
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Iron / therapeutic use
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Magnetic Resonance Imaging
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Metal Nanoparticles / chemistry
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Metal Nanoparticles / therapeutic use*
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Metal Nanoparticles / toxicity
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Mice
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Mice, Nude
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Monocarboxylic Acid Transporters / antagonists & inhibitors
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Monocarboxylic Acid Transporters / genetics
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Monocarboxylic Acid Transporters / metabolism
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Muscle Proteins / antagonists & inhibitors
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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Nanomedicine*
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Neoplasms / pathology
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Neoplasms / therapy*
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Osmotic Pressure
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Oxidative Stress / drug effects
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PC-3 Cells
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RNA Interference*
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RNA, Small Interfering / chemistry
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RNA, Small Interfering / metabolism
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RNA, Small Interfering / therapeutic use
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Transplantation, Heterologous
Substances
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Fenton's reagent
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Ferric Compounds
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Monocarboxylic Acid Transporters
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Muscle Proteins
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RNA, Small Interfering
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SLC16A4 protein, human
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ferric oxide
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Hydroxyl Radical
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Hydrogen Peroxide
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Iron