Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):71-87. doi: 10.1021/acsbiomaterials.8b01374. Epub 2019 Mar 15.
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.
将抗癌药物递送到肺部的局部给药已被证明是肺癌治疗的开创性方法。通过顺序溶剂蒸发法制备了载有全反式维甲酸 (ATRA) 和染料木黄酮 (GNS) 的混合脂质纳米核-蛋白壳纳米粒 (HLPNP)，然后通过将玉米醇溶蛋白壳沉淀在脂质核上。HLPNP 的外层蛋白壳为 ATRA/硬脂胺离子对的包封提供了额外的药物储库，并使生物素和 ATRA 能够进行双重肿瘤靶向。证实了 HLPNP 对 A549 肺癌细胞的摄取和细胞毒性活性增强。为了提高其在肺部的沉积深度，制备了双重靶向载药 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性能（MMAD=2.47μm，FPF=70.81%）。在体内，与雾化或静脉注射纳米颗粒混悬液相比，可吸入的纳米复合材料对荷肺癌小鼠具有更好的疗效。总之，可吸入的双重靶向 HLPNP 纳米复合材料为肺癌治疗提供了 GNS 和 ATRA 的局部共递药。
