Abstract：
The injective lyotropic liquid crystalline nanogels (LLCNs) were widely used in drug delivery systems. But when administered in vivo, LLCNs exposed to the biological environment interact with proteins. Recently, it has been shown that nanoparticles coated with zwitterions can inhibit their interaction with proteins. Thus, in this study, the interaction between proteins and LLCNs coated with the zwitterionic material sulfobetaine (GLLCNs@HDSB) was investigated using bovine serum albumin (BSA) as a model protein. Interestingly, it was found that GLLCNs@HDSB at higher concentrations (≥0.8 mg/mL) could block its interaction with BSA, but not at lower concentrations (<0.8 mg/mL), according to the results of ultraviolet, fluorescence, and circular dichroism spectra. In the ultraviolet spectra, the absorbance of GLLCNs@HDSB (0.8 mg/mL) was 1.9 times higher than that without the sulfobetaine coating (GLLCNs) after incubation with protein; the fluorescence quenching intensity of GLLCNs@HDSB was conversely larger than that of the GLLCNs; in circular dichroism spectra, the ellipticity value of GLLCNs@HDSB was significantly smaller than that of the GLLCNs, and the change in GLLCNs@HDSB was 10 times higher than that of the GLLCNs. Generally, nanoparticles coated with sulfobetaine can inhibit their interaction with proteins, but in this study, LLCNs showed a concentration-dependent inhibitory effect. It could be inferred that in contrast to the surface of nanoparticles covered with sulfobetaine in other cases, the sulfobetaine in this study interacted with the LLCNs and was partially inserted into the hydrophobic region of the LLCNs. In conclusion, this study suggests that coating-modified nanoparticles do not necessarily avoid interacting with proteins, and we should also study coating-modified nanoparticles interacting with proteins both in vitro and in vivo. In the future, finding a coating material to completely inhibit the interaction between LLCNs and proteins will generate a great impetus to promote the clinical transformation of LLCNs.
摘要：
注射溶致液晶纳米凝胶(LLCNs)被广泛用于药物递送系统中。但是当体内给药时，暴露于生物环境的LLCN与蛋白质相互作用。最近,研究表明，涂有两性离子的纳米粒子可以抑制它们与蛋白质的相互作用。因此，在这项研究中，使用牛血清白蛋白（BSA）作为模型蛋白，研究了蛋白质与两性离子材料磺基甜菜碱（GLLCNs@HDSB）包被的LLCNs之间的相互作用。有趣的是,发现较高浓度（≥0.8mg/mL）的GLLCNs@HDSB可以阻断其与BSA的相互作用，但在较低的浓度(<0.8mg/mL)下，根据紫外线的结果，荧光，和圆二色性光谱。在紫外光谱中，与蛋白质孵育后，GLLCNs@HDSB（0.8mg/mL）的吸光度比没有磺基甜菜碱涂层（GLLCNs）的吸光度高1.9倍；GLLCNs@HDSB的荧光猝灭强度相反地大于GLLCNs的荧光猝灭强度；在圆二色光谱中，GLLCNs@HDSB的椭圆率值明显小于GLLCNs,GLLCNs@HDSB的变化是GLLCNs的10倍。一般来说,用磺基甜菜碱包被的纳米颗粒可以抑制它们与蛋白质的相互作用，但是在这项研究中，LLCNs表现出浓度依赖性抑制作用。可以推断，与其他情况下覆盖有磺基甜菜碱的纳米颗粒表面相反，本研究中的磺基甜菜碱与LLCNs相互作用，并部分插入LLCNs的疏水区域。总之,这项研究表明，涂层修饰的纳米颗粒不一定避免与蛋白质相互作用，我们还应该研究涂层修饰的纳米颗粒在体外和体内与蛋白质的相互作用。在未来,找到完全抑制LLCNs与蛋白质相互作用的涂层材料,将对促进LLCNs的临床转化产生巨大的推动作用。
