Localized pulmonary delivery of anticancer agents to lungs has proven to be pioneering approach for lung cancer therapy. Hybrid lipid nanocore-protein shell nanoparticles (HLPNPs) coloaded with all-trans retinoic acid (ATRA) and genistein (GNS) were prepared via sequential solvent evaporation followed by nanoprecipitation of zein shell onto the lipid core. The outer protein shell of HLPNPs provided additional drug reservoir for encapsulation of ATRA/stearyl amine ion pair and enabled dual tumor-targeting with biotin and ATRA. Enhanced uptake and cytotoxic activity of HLPNPs against A549 lung cancer cells was confirmed. To improve their deep lung deposition, dual-targeted drug-loaded HLPNP nanocomposites were fabricated. The nanocomposites prepared using mannitol/HPβCD/leucine demonstrated favorable aerosolization (MMAD = 2.47 μm and FPF = 70.81%). In vivo, the inhalable nanocomposites were superior to aerosolized or i.v. nanoparticle suspension against lung carcinoma bearing mice. Overall, inhalable dual-targeted HLPNPs nanocomposites provided localized codelivery of GNS and ATRA for lung cancer therapy.

中文翻译：

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可吸入双靶杂交脂质纳米核-蛋白质壳复合材料，可将金雀异黄素和全反式维甲酸联合递送至肺癌细胞

肺部抗癌剂向肺的局部肺输送已被证明是肺癌治疗的开创性方法。通过顺序蒸发溶剂，然后将玉米醇溶蛋白壳纳米沉淀到脂质核上，制备了与全反式视黄酸（ATRA）和染料木黄酮（GNS）共同负载的杂化脂质纳米核-蛋白壳纳米颗粒（HLPNPs）。HLPNPs的外壳蛋白为ATRA /硬脂胺离子对的包封提供了额外的药物库，并实现了生物素和ATRA的双重肿瘤靶向。证实了HLPNP对A549肺癌细胞的摄取和细胞毒活性增强。为了改善其深部肺部沉积，制备了双靶点载药的HLPNP纳米复合材料。使用甘露醇/HPβCD/亮氨酸制备的纳米复合材料表现出良好的雾化作用（MMAD = 2.47μm，FPF = 70.81％）。在体内，可吸入的纳米复合材料优于雾化的或静脉注射的纳米颗粒悬浮液对患有肺癌的小鼠具有抑制作用。总体而言，可吸入的双重靶向HLPNPs纳米复合材料为肺癌治疗提供了GNS和ATRA的局部代码传递。