Abstract
A tumor redox-activatable micellar nanoplatform based on the naturally occurring biomacromolecule hyaluronic acid (HA) was developed for complementary photodynamic/chemotherapy against CD44-positive tumors. Here HA was first conjugated with l-carnitine (Lc)-modified zinc phthalocyanine (ZnPc) via disulfide linkage and then co-assembled with tirapazamine (TPZ) to afford the physiologically stable micellar nanostructure. The mitochondria-targeted photodynamic activity of ZnPc-Lc could efficiently activate the mitochondrial apoptosis cascade and deplete the oxygen in the tumor intracellular environment to amplify the hypoxia-dependent cytotoxic effect of TPZ.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Biopolymers / chemistry*
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Carnitine / chemistry
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Cell Line, Tumor
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Humans
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Hyaluronic Acid / chemistry
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Indoles / chemistry
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Infrared Rays
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Isoindoles
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Mice
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Micelles*
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Nanostructures / chemistry*
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Neoplasms / drug therapy
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Neoplasms / pathology
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Organometallic Compounds / chemistry
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Oxidation-Reduction
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Photochemotherapy
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Photosensitizing Agents / chemistry
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Photosensitizing Agents / pharmacology
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Photosensitizing Agents / therapeutic use
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Tirapazamine / chemistry
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Tirapazamine / pharmacology
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Tirapazamine / therapeutic use
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Transplantation, Heterologous
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Zinc Compounds
Substances
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Antineoplastic Agents
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Biopolymers
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Indoles
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Isoindoles
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Micelles
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Organometallic Compounds
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Photosensitizing Agents
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Zinc Compounds
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Zn(II)-phthalocyanine
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Tirapazamine
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Hyaluronic Acid
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Carnitine