HER2-specific affibody-conjugated thermosensitive liposomes (Affisomes) for improved delivery of anticancer agents.

摘要: Thermosensitive liposomes are attractive vehicles for the delivery and release of drugs to tumors. To improvethe targeting efficacy breast cancer treatment, an 8.3-kDa HER2-specific Affibody molecule (Z(HER2:342)-Cys) was conjugated surface liposomes. The effects this modification on physical characteristics stability resulting nanoparticles denoted as "Affisomes" were investigated. small unilamellar vesicle (SUV) (80-100 nm) a diameter consisting dipalmitoyl phosphatidylcholine (DPPC, Tm 41 degrees C) matrix lipid maleimide-conjugated pegylated phospholipid (DSPE-MaL-PEG2000) prepared by probe sonication. Fluorescent probes incorporated into biophysical and/or biochemical analysis triggered-release assays. these via its C-terminal cysteine incubation in presence reducing agent (e.g., tributylphosphine) 16-20 hours under argon atmosphere. Lipid-conjugated affibody visible 11.3-kDa band 4-12% Bis/Tris gel conditions. conjugation yields approximately 70% at protein-lipid ratio 20 microg/mg, with average number 200 molecules per Affisome. thermosensitive did not have any significant effect hydrodynamic size distribution Thermosensitivity Affisomes determined monitoring entrapped calcein (a water-soluble fluorescent probe, lambdaex/em 490/515 function temperature. Calcein released from (thermosensitive affibody-Targeted SUV) well nontargeted SUV without affibody) temperature-dependent manner, optimal leakage (90-100%) C. In contrast, Egg phosphatidyl choline (Egg PC, 0 similar conditions only 5-10% Affisomes, when stored room temperature, retained > 90% up 7 days. Moreover, phosphate-buffered saline, supplemented 10% heat-inactivated serum (fetal bovine serum) result destabilization Therefore, present promising, novel drug-delivery candidates targeting.