隐形PEG-PHDCA纳米囊泡：PEG的相对分子质量对体外补体消耗和巨噬细胞吞噬的影响

目的考察不同PEG相对分子质量对包载羟基喜树碱的PEG-PHDCA纳米囊泡的理化性质、体外补体活性和巨噬细胞吞噬影响。方法对纳米囊泡的理化性质包括粒径、zeta电位、表面固有水化层厚度、PEG表面密度等进行表征，进一步阐明其理化性质与纳米囊泡的补体消耗和巨噬细胞吞噬之间的关系。结果PEG_{10 000}-PHDCA具有比其他两组更松弛的结构，PEG链表面密度最小；进一步通过固有水化层厚度的测定进行构型模拟表明：囊泡表面PEG发生折叠，柔韧性下降，导致其较差的隐形效果。与PEG_{2 000}-PHDCA囊泡比较，PEG_{5 000}-PHDCA囊泡显示了更佳的zeta电位(-10.03 mV)和水化层厚度(4.20 nm)，PEG的表面密度也在较佳范围内(0.49 PEG·nm^-2)，这些理化性质赋予其最佳的规避补体消耗和巨噬细胞吞噬的作用。结论过长的PEG链对囊泡表面的修饰并不利于其隐形效果，PEG_{5 000}-PHDCA修饰的纳米囊泡具有最佳的规避补体介导和巨噬细胞吞噬作用。

Stealth PEG-PHDCA niosomes: effects of chain length of PEG on niosomes in vitro complement consumption and phagocytic uptake

AIM: Poly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied. METHODS: The physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated. RESULTS: Experimental results showed that PEG10,000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10,000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2,000-PHDCA, PEG5,000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4.20 nm, less negative zeta potential of -10.03 mV, and enhanced PEG surface density of 0.49 PEG x nm(-2), leading to the best effects of reduction of complement consumption and phagocytic uptake. CONCLUSION: Excessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5,000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.