Poly(L-lactide)-vitamin E TPGS nanoparticles enhanced the cytotoxicity of doxorubicin in drug-resistant MCF-7 breast cancer cells.
Multiple drug resistance (MDR) seriously reduces the efficacy of many chemotherapeutic agents for cancer. P-Glycoprotein, an efflux pump overexpressed on the cell surface, plays an important role in drug resistance, but several surfactants, such as vitamin E TPGS, can inhibit P-glycoprotein. In this study, a polylactide-surfactant block copolymer poly(l-lactide)-vitamin E TPGS (PLA-TPGS) was synthesized using bidentate sulfonamide zinc ethyl complex as an efficient catalyst, and its self-assembled nanoparticles were used as carriers of doxorubicin. We first found that the activity of P-glycoprotein in drug-resistant breast cancer MCF-7/ADR cells was decreased after incubation with PLA-TPGS nanoparticles. In addition, the nuclear accumulation and cytotoxicity of doxorubicin were significantly increased by encapsulation into the nanoparticles. The enhanced efficacy of the doxorubicin-loaded PLA-TPGS nanoparticles may result from the combination of inhibition of efflux and increased entry of doxorubicin into the nucleus in drug-resistant MCF-7/ADR cells. Therefore, this innovative delivery system has potential to act as a nanomedicine for therapy of both drug-sensitive and drug-resistant cancer.
Li
Po-Yu
PY
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan.
Lai
Ping-Shan
PS
Hung
Wen-Chou
WC
Syu
Wei-Jhe
WJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002384:Catalysis; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D013386:Succinates; C514223:poly(lactide)-tocopheryl polyethylene glycol succinate; D014810:Vitamin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; C014225:tocophersolan