The blood brain barrier separates the circulating blood from the extracellular fluid in the central nervous system and thus presents an essential obstacle to brain transport of therapeutics. Herein, we report on an effective brain-targeted drug delivery system that combines a robust red blood cell membrane-coated nanoparticle (RBCNP) with a unique neurotoxin-derived targeting moiety. The RBCNPs retain the complex biological functions of natural cell membranes while exhibiting physicochemical properties that are suitable for effective drug delivery. CDX peptide is derived from candoxin and shows high binding affinity with nicotinic acetylcholine receptors (nAChRs) expressed on the surface of brain endothelial cells. Through a facile yet robust approach, we successfully incorporate ^DCDX peptides onto the surface of RBCNPs without compromising the peptide's brain targeting ability. The resulting ^DCDX-RBCNPs show promising brain targeting efficiency both in vitro and in vivo. Using a glioma mouse model, we demonstrate that doxorubicin-loaded ^DCDX-RBCNPs have superior therapeutic efficacy and markedly reduced toxicity as compared to the nontargeted drug formulations. While RBCNPs are used as a model system to evaluate the surface modification approach, the reported method can be readily generalized to various types of cell membrane-derived nanocarriers for broad medical applications.

血脑屏障将循环血液从中枢神经系统中的细胞外液中分离出来，因此对治疗药物的脑部运输提出了重要障碍。在本文中，我们报告了一种有效的针对大脑的药物递送系统，该系统将强大的红细胞膜涂层纳米颗粒（RBCNP）与独特的神经毒素衍生的靶向部分相结合。RBCNP保留了天然细胞膜的复杂生物学功能，同时展现出适合有效药物递送的理化特性。CDX肽衍生自candoxin，并与脑内皮细胞表面表达的烟碱型乙酰胆碱受体（nAChRs）具有高结合亲和力。通过简便而强大的方法，我们成功地将^D将CDX肽粘贴到RBCNPs的表面上，而不会损害该肽的大脑靶向能力。所得的^D CDX-RBCNPs在体外和体内均显示出有希望的脑靶向效率。使用神经胶质瘤小鼠模型，我们证明了与非靶向药物制剂相比，阿霉素负载的^D CDX-RBCNPs具有优越的治疗功效并显着降低了毒性。虽然RBCNPs被用作评估表面改性方法的模型系统，但已报道的方法可以很容易地推广到各种类型的细胞膜衍生的纳米载体，从而在广泛的医学应用中使用。