Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface‐grafted poly(ethylene glycol)
[摘要] Plasma-stable liposomes (100 nm) were prepared from dioleoylphosphatidylethanolamine (DOPE) and 3–6 mol% of a new disulfide-linked poly(ethylene glycol)-phospholipid conjugate (mPEG-DTP-DSPE). In contrast to similar preparations containing non-cleavable PEG-phospholipid conjugate, thiolytic cleavage of the grafted polymer chains facilitated rapid and complete release of the liposome contents. Furthermore, the detachment of PEG from DOPE liposomes resulted in liposomal fusion. Finally, while formulation of pH-sensitive DOPE/cholesterol hemisuccinate liposomes with mPEG-DTP-DSPE abolished the pH sensitivity, cleavage of the PEG chains completely restored this property. These are the first examples of new useful properties of liposomes grafted with cleavable polymer.
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[效力级别] [学科分类] 生物化学/生物物理
[关键词] Liposomes;Drug targeting;Phosphatidylethanolamine;Polyethylene glycol derivatives;Membrane fusion;Disulfide bond;CHEMS;cholesteryl hemisuccinate;Chol;cholesterol;DOPC;1;2-dioleoyl-sn-glycerophosphorylcholine;DOPE;1;2-dioleoyl-sn-glycero-3-phosphorylethanolamine;DPX;p-xylene-bis-pyridinium bromide;DSPE;1;2-distearoyl-sn-glycero-3-phosphorylethanolamine;DTSP;dithiobis(succinimidyl propionate);DTT;dithiothreitol;HEPEN-NS;20 mM N-hydroxyethyl-piperazinoethanesulfonic acid;144 mM NaCl;pH 7.2;HPTS;trisodium 8-hydroxypyrenetrisulfonate;MES;N-morpholinoethanesulfonic acid;NBD-PE;N-(7-nitro-2-1;3-benzoxadiazol-4-yl)-phosphatidylethanolamine (egg transphosphatidylated);PEG;poly(ethylene glycol);mPEG;methoxypoly(ethylene glycol);mPEG-DSPE;N-(ω-methoxypoly(oxyethylene)-α-oxycarbonyl)-DSPE;mPEG-DTP-DSPE;N-(2-(ω-methoxypoly(oxyethylene)-α-aminocarbonyl)ethylene-dithiopropionyl)-DSPE;mPEG-DTP-OSu;N-succinimidyl-2-(ω-methoxypoly(oxythelene)-α-aminocarbonyl)ethyl-dithipropionate;PL;phospholipid;Rho-PE;N-lissamine-rhodamine B sulfonyl-phosphatidylethanolamine (egg transphosphatidylated);RES;reticuloendothelial system;SSL;sterically stabilized liposomes [时效性]
