Star-shape copolymer of lysine-linked di-tocopherol polyethylene glycol 2000 succinate for doxorubicin delivery with reversal of multidrug resistance.
作者： Jinling Wang , Jin Sun , Qin Chen , Ying Gao , Lin Li
DOI: 10.1016/J.BIOMATERIALS.2012.06.019
关键词:
摘要: Abstract A star-shape copolymer of nanostructure-forming material, P-glycoprotein (P-gp) reversible inhibitor and anticancer enhancer, lysine-linked di-tocopherol polyethylene glycol 2000 succinate (PLV 2K ), was synthesized to overcome multidrug resistance (MDR) in cancer chemotherapy. The critical micellar concentration PLV as low 1.14 μg/mL, which can endow nanoassemblies good physical stability. Doxorubicin (DOX) encapsulated into the hydrophobic core -DOX), with encapsulation efficiency high 94.5% a particle size 16.4 nm. DOX released from -DOX nanomicelles pH-dependent, ensures micelles stable blood circulation releases within tumor cells. Facilitated by cytotoxicity uncompetitive P-gp ATPase inhibition , showed greater compared solution increased intracellular accumulation resistant MCF-7/Adr were uptaken cells via macropinocytosis caveolae-mediated endocytosis, further facilitate escapement efflux. efficacy in vivo evaluated 4T1-bearing mice more effective than TPGS-DOX solution. In summary, has striking functions such efficacy, could be promising nanocarrier improving chemotherapy drugs.
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