Abstract
As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.
Keywords:
Anti-metastasis; Chemo-photodynamic therapy; Chemosensitizer; Chondroitin sulfate; Multidrug resistance; Reactive oxygen species.
Copyright © 2020 Elsevier Ltd. All rights reserved.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Animals
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology
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Breast Neoplasms / therapy*
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Cell Proliferation / drug effects
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Cell Proliferation / radiation effects
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Chlorophyllides
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Chondroitin Sulfates / chemistry
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Combined Modality Therapy
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Doxorubicin / pharmacology
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Drug Carriers*
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Drug Resistance, Neoplasm / radiation effects*
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Female
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Gene Expression
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Humans
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Infrared Rays / therapeutic use
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Lasers
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Lung Neoplasms / genetics
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Lung Neoplasms / secondary
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Lung Neoplasms / therapy*
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MCF-7 Cells
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry
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Paclitaxel / pharmacology
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Photosensitizing Agents / pharmacology*
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Porphyrins / pharmacology
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Quercetin / pharmacology
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Reactive Oxygen Species / agonists
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Reactive Oxygen Species / metabolism
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Xenograft Model Antitumor Assays
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Chlorophyllides
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Drug Carriers
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Photosensitizing Agents
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Porphyrins
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Reactive Oxygen Species
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phytochlorin
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Doxorubicin
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Chondroitin Sulfates
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Quercetin
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Paclitaxel