文献：Esterase-catalyzed dePEGylation of pH-sensitive vesicles modified with cleavable PEG-lipid derivatives

作者：Huan Xu a b, Yihui Deng a, Dawei Chen a, Weiwei Hong a, Yi Lu a, Xiaohui Dong 

文献链接：https://www.sciencedirect.com/science/article/abs/pii/S0168365908002629

To make vesicles for the better controlled content release, we modified cholesteryl hemisuccinate (CHEMS)-derived vesicles with PEG-lipid derivatives. Two cholesterol analogs, cholesteryl hemisuccinate (CHEMS) and cholesteryl chloroformate (CHM), have been conjugated to the polyethylene glycol (PEG) via their ester bonds for the vesicle modifications, so the PEGs can be cleaved by esterases. The effects of PEG-lipid proportions, serum concentrations and the lipid types on the esterase-catalyzed cleavage of PEG polymer off the vesicles surface were determined. We observed that PEG cleavages decreased as the molar ratios of the PEG-lipids in vesicles increased; on the other hand, PEG cleavages gradually increased with the increased serum concentrations. In contrast to conventional long circulation materials mPEG-DSPE and mPEG-CHOL, the two new conjugates enabled higher degrees of PEG cleavages from modified vesicles. After incubation in the serum at acidic conditions, esterase-catalyzed dePEGylation destabilized these vesicles, increasing the mean particle sizes and promoting content releases. These results suggested that ester linkages between the PEG and lipid anchors allow faster content releases in the suitable conditions. Together, the two esterase cleavable PEG-lipid conjugations may be applied not only to stabilize vesicles and prolong their circulation time, but also to provide more efficient content releases by the esterase controlled dePEGylation.

为了制备更好地控制内容物释放的囊泡，我们用PEG脂质衍生物修饰了胆固醇半琥珀酸盐（CHEMS）衍生的囊泡。两种胆固醇类似物，胆固醇半琥珀酸酯（CHEMS）和胆固醇氯甲酸酯（CHM），通过其酯键与聚乙二醇（PEG）结合进行囊泡修饰，因此PEG可以被酯酶切割。

测定了PEG脂质比例、血清浓度和脂质类型对酯酶催化PEG聚合物从囊泡表面切割的影响。我们观察到，随着囊泡中PEG脂质摩尔比的增加，PEG裂解减少；另一方面，PEG裂解随着血清浓度的增加而逐渐增加。

与传统的长循环材料mPEG-DSPE和mPEG-CHOL相比，这两种新的偶联物能够从修饰的囊泡中实现更高程度的PEG裂解。在酸性条件下在血清中孵育后，酯酶催化的去聚乙二醇化使这些囊泡失稳，增加了平均粒径并促进了内容物的释放。

这些结果表明，PEG和脂质锚之间的酯键在合适的条件下允许更快的内容物释放。这两种酯酶可切割的PEG-脂质偶联物可以一起应用，不仅可以稳定囊泡并延长其循环时间，还可以通过酯酶控制的去聚乙二醇化提供更有效的内容物释放。

相关推荐：

C18-PEGn-OPSS

C18-PEGn-SH (SH: Thiol)

mPEG-Cholesterol (mPEG-CLS)

mPEG-CONH-C12

mPEG-CONH-C16

mPEG-CONH-C18

mPEG-DMPE

mPEG-DSPE

mPEG-O-C12

mPEG-O-C16

mPEG-O-C18

mPEG-Unsaturated Fatty Acid

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