The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood–brain barrier and attenuates their targeting ability to brain tumor
The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood–brain barrier and attenuates their targeting ability to brain tumor
复制标题
蛋白冠阻碍转铁蛋白修饰纳米粒子通过血脑屏障的转胞吞作用，并削弱其对脑肿瘤的靶向能力
DOI：
10.1016/j.biomaterials.2021.120888
复制
发表时间：
2021
期刊：
影响因子：
14
通讯作者：
Huile Gao
中科院分区：
文献类型：
--
作者：
Wei Xiao;Yazhen Wang;Huilin Zhang;Yuwei Liu;Rou Xie;Xueqin He;Yang Zhou;Luqing Liang;Huile Gao
预期纳米颗粒（NP）上的靶向配体的修饰将增强治疗剂向患病组织的递送。然而，一旦暴露于血流中，NPs可以立即吸附蛋白质以形成“蛋白质冠”，这可能极大地阻碍靶向配体与其受体结合。对于脑靶向递送，纳米治疗剂必须穿过血脑屏障（BBB）进入脑实质，然后靶向病变细胞。然而，它仍然难以捉摸，除了受体识别，蛋白质冠是否可以影响其他过程中涉及血脑屏障转胞吞作用，如内吞作用，细胞内运输，和胞吐。此外，转胞吞作用后纳米颗粒对病变细胞的靶向能力仍不清楚。在此，转铁蛋白（Tf），脑靶向配体，耦合到纳米粒子，以评估血脑屏障转胞吞和脑肿瘤靶向能力。结果表明，体外和体内蛋白冠对受体靶向、溶酶体逃逸和血脑屏障转胞吞作用有不同的影响，体外蛋白冠可消除Tf介导的上述过程，而体内蛋白冠则减弱这些作用。在穿过血脑屏障后，Tf保留了其对脑肿瘤细胞的靶向特异性。总之，这些结果揭示了几种结合的载脂蛋白，特别是载脂蛋白A-I，可能有助于NPs穿过BBB，从而为脑靶向递送的发展提供了新的见解。
The modification of targeting ligands on nanoparticles (NPs) is anticipated to enhance the delivery of therapeutics to diseased tissues. However, once exposed to the blood stream, NPs can immediately adsorb proteins to form the “protein corona,” which may greatly hinder the targeting ligand from binding to its receptor. For brain-targeting delivery, nanotherapeutics must traverse the blood–brain barrier (BBB) to enter the brain parenchyma and then target the diseased cells. However, it remains elusive whether, apart from receptor recognition, the protein corona can affect other processes involved in BBB transcytosis, such as endocytosis, intracellular trafficking, and exocytosis. Furthermore, the targeting ability of NPs toward diseased cells after transcytosis remains unclear. Herein, transferrin (Tf), a brain-targeting ligand, was coupled to NPs to evaluate BBB transcytosis and brain tumor targeting ability. Different impacts of thein vitroandin vivoprotein corona on receptor targeting, lysosomal escape, and BBB transcytosis were found. Thein vitroprotein corona abolished the Tf-mediated effects of the abovementioned processes, whereas thein vivoprotein corona attenuated these effects. After crossing the BBB, Tf retained its targeting specificity towards brain tumor cells. Together, these results revealed that several bound apolipoproteins, especially apolipoprotein A-I, may help NPs traverse the BBB, thereby providing novel insights into the development of brain-targeted delivery.