Poly(ethylene glycol)-Lipid Conjugates Regulate the Calcium-Induced Fusion of Liposomes Composed of Phosphatidylethanolamine and Phosphatidylserine

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• 作者：John W. Holland ; Cathy Hui ; Pieter R. Cullis ; and Thomas D. Madden
• 刊名：Biochemistry
• 出版年：1996
• 出版时间：February 27, 1996
• 年：1996
• 卷：35
• 期：8
• 页码：2618 - 2624
• 全文大小：373K
• 年卷期：v.35,no.8(February 27, 1996)
• ISSN：1520-4995

文摘

The effect of poly(ethylene glycol)-lipid (PEG-lipid)conjugates on liposomal fusion wasinvestigated. Incorporation of PEG-lipids into large unilamellarvesicles (LUVs) composed of equimolarphosphatidylethanolamine (PE) and phosphatidylserine (PS) inhibitedcalcium-induced fusion. The degreeof inhibition increased with increasing molar ratio of the PEGconjugate and with increasing size of thePEG moiety. Inhibition appeared to result from the steric barrieron the surface of the liposomes whichopposed apposition of bilayers and interbilayer contact. In thepresence of a large excess of neutralacceptor liposomes, however, fusogenic activity was restored. Therate of fusion under these conditionsdepended on the initial molar ratio of the PEG conjugate in the PE:PSvesicles and the length and degreeof saturation of the acyl chains which composed the lipid anchor.These results are consistent withspontaneous transfer of the PEG-lipid from PE:PS LUVs to the neutrallipid sink reducing the stericbarrier and allowing fusion of the PE:PS LUVs. The primarydeterminant of the rate of fusion was therate of transfer of the PEG-lipid, indicating that liposomal fusioncould be programmed by incorporationof appropriate PEG-lipid conjugates. Interestingly, increasingthe size of the PEG group did not appearto affect the rate of fusion. The implications of these resultswith respect to the design of fusogenicliposomal drug delivery systems are discussed.