Abstract
An ideal cancer therapeutic strategy should not only reverse multidrug resistance (MDR), but also prevent cancer metastasis. In this study, bovine serum albumin (BSA) was hybridized with Mn2+via biomineralization to develop a hybrid protein oxygen nanocarrier, which contained doxorubicin (DOX) and small interfering RNA (siRNA). The nanohybrid has the function of producing oxygen and chemotherapy synergistic gene therapy. FA-BSA-MnO2/DOX/siRNA was favorable for increasing the sensitivity of MCF-7/ADR cells to DOX. Moreover, FA-BSA-MnO2/DOX/siRNA NPs were also able to generate oxygen (O2) by reaction with endogenous hydrogen peroxide (H2O2) in tumor, thereby down-regulating the expression of hypoxia inducible factor-1α (HIF-1α), and then the expression of the vascular endothelial growth factor (VEGF) was down-regulated. At the same time, siRNA can directly or indirectly suppress the expression of the VEGF and HIF-1α. Therefore, the combination of two pathways and the chemo-gene therapy strategy can interactively overcome tumor hypoxia-associated MDR and metastasis, which will enhance therapeutic efficacy in the future.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use*
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Breast Neoplasms / drug therapy*
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Cattle
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Cell Movement / drug effects
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Down-Regulation / drug effects
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Doxorubicin / therapeutic use
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Drug Carriers / chemistry*
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Drug Carriers / toxicity
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Drug Resistance, Multiple / drug effects*
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Drug Resistance, Neoplasm / drug effects*
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Female
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Folic Acid / chemistry
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Folic Acid / toxicity
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Humans
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Hydrogen Peroxide / chemistry
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Hydrogen Peroxide / metabolism
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Hydrogen-Ion Concentration
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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MCF-7 Cells
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Manganese Compounds / chemistry
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Metal Nanoparticles / chemistry*
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Metal Nanoparticles / toxicity
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Mice, Inbred BALB C
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Neoplasm Metastasis / prevention & control
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Oxides / chemistry
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Oxides / toxicity
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Oxygen / metabolism
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RNA, Small Interfering / therapeutic use
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Serum Albumin, Bovine / chemistry
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Serum Albumin, Bovine / toxicity
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Antineoplastic Agents
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Drug Carriers
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Manganese Compounds
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Oxides
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RNA, Small Interfering
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Serum Albumin, Bovine
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Doxorubicin
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Folic Acid
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Hydrogen Peroxide
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Oxygen
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manganese dioxide