Zhong Ziqiao, Chen Zhiwei, Xie Yuke, Wang Wenhao, Huang Zhengwei, Huang Ying, Wu Chuanbin, Pan Xin
College of Pharmacy, Jinan University, Guangzhou 511443, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Gels. 2022 Oct 14;8(10):653. doi: 10.3390/gels8100653.
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.
注射型溶致液晶纳米凝胶（LLCNs）被广泛应用于药物递送系统。但在体内给药时，暴露于生物环境中的LLCNs会与蛋白质相互作用。最近有研究表明，包覆两性离子的纳米颗粒可以抑制它们与蛋白质的相互作用。因此，在本研究中，以牛血清白蛋白（BSA）作为模型蛋白，研究了蛋白质与包覆两性离子材料磺基甜菜碱的LLCNs（GLLCNs@HDSB）之间的相互作用。有趣的是，根据紫外、荧光和圆二色光谱的结果发现，较高浓度（≥0.8 mg/mL）的GLLCNs@HDSB能够阻断其与BSA的相互作用，但较低浓度（<0.8 mg/mL）时则不能。在紫外光谱中，与蛋白质孵育后，GLLCNs@HDSB（0.8 mg/mL）的吸光度比未包覆磺基甜菜碱的GLLCNs高1.9倍；GLLCNs@HDSB的荧光猝灭强度反而比GLLCNs更大；在圆二色光谱中，GLLCNs@HDSB的椭圆率值明显小于GLLCNs，且GLLCNs@HDSB的变化比GLLCNs高10倍。一般来说，包覆磺基甜菜碱的纳米颗粒可以抑制它们与蛋白质的相互作用，但在本研究中，LLCNs表现出浓度依赖性抑制作用。可以推断，与其他情况下包覆磺基甜菜碱的纳米颗粒表面不同，本研究中的磺基甜菜碱与LLCNs相互作用并部分插入到LLCNs的疏水区域。总之，本研究表明，包覆改性的纳米颗粒不一定能避免与蛋白质相互作用，我们还应在体外和体内研究包覆改性的纳米颗粒与蛋白质的相互作用。未来，找到一种能完全抑制LLCNs与蛋白质相互作用的包覆材料将对推动LLCNs的临床转化产生巨大的推动作用。
