液晶自组装纳米组装体（LLCNs）是由两性分子在脂质、稳定剂和/或表面活性剂以及水溶性介质/分散剂混合物中形成的内部自组装（ISA）体。LLCNs是一类独特的纳米组装体，在广泛的生物医学功能中具有多种应用。然而，它们是一种纳米系统，尚未完全探索用于靶向乳腺癌的系统性治疗。本研究制备了用于共递送吉西他滨和胡葱醌（Gem-TQ）的LLCNs，其由大豆磷脂酰胆碱（SPC）、恶二醇三酸酯（PHYT）或单硬脂酸甘油酯（MYVR）以及优化比例的柠檬酸和脂肪酸酯基乳化剂（格林斯泰德柠檬酸酯）或三嵌段共聚物F127制备而成。所确定的动力学粒径小于400 nm（在96-365 nm之间），并且一系列纳米制剂呈负电荷表面。小角X射线散射（SAXS）谱图指出非层状相包括六角、立方和胶束相。另外，共加载纳载体系统SPC/citrem/Gem-TQ六角体呈现出高捕获效率，吉西他滨和胡葱醌的封装率分别为98.3±0.1%和99.5±0.1%。MCF10A细胞中对于SPC-citrem六角体的低细胞毒性与斑马鱼胚胎中血液和生物相容性的观察一致，观察时长可达到孵化后96 h（hpf）。SPC/citrem/Gem-TQ六角体在MCF7乳腺癌细胞中表现出IC50值为24.7±4.2 μM，持续处理24h后仍保持吉西他滨和胡葱醌间中度协同作用（CI=0.84）。综上所述，具有生物相容性的SPC/citrem/Gem-TQ六角体可以进一步发展为一种多功能治疗纳米递药策略，通过纳入靶向配基实现对乳腺癌细胞的靶向治疗。

Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.