title: Reversal of doxorubicin-resistance by multifunctional nanoparticles in MCF-7/ADR cells.
abstract: The efficacy of many chemotherapeutic agents is reduced in cells that have developed multiple drug resistance (MDR). To address this important problem, a biodegradable polymer was coupled to a photosensitizer and the resulting photosensitizer-nanoparticles were loaded with the chemotherapeutic agent doxorubicin. The combination of photosensitizer and chemotherapeutic agent had a synergistic action on a doxorubicin-resistant breast cancer MCF-7 cell line. To increase the effectiveness of this combination, d-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS), an inhibitor of the multidrug transporter overproduced in these resistant cells, was added during the formation of the nanoparticles. The insertion of TPGS decreased the P-glycoprotein activity, increased the intracellular accumulation doxorubicin, and also increased the therapeutic efficacy of the resulting nanoparticles. Both TPGS and irradiation of the photoreactive nanoparticles caused doxorubicin to move from the cytoplasm to the nucleus. This combination of photodynamic activity in a powerful nanocarrier loaded with the chemotherapeutic agent doxorubicin can be used to deliver two types of cancer therapy simultaneously, and the addition of TPGS can further enhance the entry of doxorubicin into the nucleus. Therefore, this innovative delivery system can act as a potential nanomedicine for both drug-sensitive and drug-resistant cancer therapy.
authors: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei.
authors: Ming-Jium
authors: MJ
authors: Shieh
authors: Chia-Yen
authors: CY
authors: Hsu
authors: Ling-Yi
authors: LY
authors: Huang
authors: Hsuan-Ying
authors: HY
authors: Chen
authors: Fei-Hong
authors: FH
authors: Huang
authors: Ping-Shan
authors: PS
authors: Lai
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003594:Cytoplasmic Granules / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008027:Light; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry; D014700:Verapamil / Q000494:pharmacology; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D004338:Drug Combinations; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011091:Polyesters; D011108:Polymers; D011166:Porphyrins; D014810:Vitamin E; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin; D014700:Verapamil; C014225:tocophersolan; C007740:fluorexon