文獻：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 

文獻鏈接：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.

為了制備更好地控制內(nèi)容物釋放的囊泡，我們用PEG脂質(zhì)衍生物修飾了膽固醇半琥珀酸鹽（CHEMS）衍生的囊泡。兩種膽固醇類似物，膽固醇半琥珀酸酯（CHEMS）和膽固醇氯甲酸酯（CHM），通過其酯鍵與聚乙二醇（PEG）結(jié)合進行囊泡修飾，因此PEG可以被酯酶切割。

測定了PEG脂質(zhì)比例、血清濃度和脂質(zhì)類型對酯酶催化PEG聚合物從囊泡表面切割的影響。我們觀察到，隨著囊泡中PEG脂質(zhì)摩爾比的增加，PEG裂解減少；另一方面，PEG裂解隨著血清濃度的增加而逐漸增加。

與傳統(tǒng)的長循環(huán)材料mPEG-DSPE和mPEG-CHOL相比，這兩種新的偶聯(lián)物能夠從修飾的囊泡中實現(xiàn)更高程度的PEG裂解。在酸性條件下在血清中孵育后，酯酶催化的去聚乙二醇化使這些囊泡失穩(wěn)，增加了平均粒徑并促進了內(nèi)容物的釋放。

這些結(jié)果表明，PEG和脂質(zhì)錨之間的酯鍵在合適的條件下允許更快的內(nèi)容物釋放。這兩種酯酶可切割的PEG-脂質(zhì)偶聯(lián)物可以一起應(yīng)用，不僅可以穩(wěn)定囊泡并延長其循環(huán)時間，還可以通過酯酶控制的去聚乙二醇化提供更有效的內(nèi)容物釋放。

相關(guān)推薦：

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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