Transportation of Single-Domain Antibodies through the Blood-Brain Barrier

被引:56
作者
Ruiz-Lopez, Eduardo [1 ,2 ]
Schuhmacher, Alberto J. [2 ]
机构
[1] Inst Invest Sanitaria Aragon IIS Aragon, Mol Oncol Grp, Zaragoza 50009, Spain
[2] Fdn Aragonesa Invest & El Desarrollo ARAID, Zaragoza 500018, Spain
关键词
single-domain antibodies; nanobody; VNAR; blood-brain barrier; transcytosis; nanoparticles; cell-penetrating peptides; carriers; CONVECTION-ENHANCED DELIVERY; CENTRAL-NERVOUS-SYSTEM; NEONATAL FC-RECEPTOR; DRUG-DELIVERY; HEAVY-CHAIN; IN-VITRO; GLIOBLASTOMA-MULTIFORME; BRADYKININ AGONIST; MEDIATED DELIVERY; KINETIC-ANALYSIS;
D O I
10.3390/biom11081131
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Single-domain antibodies derive from the heavy-chain-only antibodies of Camelidae (camel, dromedary, llama, alpaca, vicunas, and guananos; i.e., nanobodies) and cartilaginous fishes (i.e., VNARs). Their small size, antigen specificity, plasticity, and potential to recognize unique conformational epitopes represent a diagnostic and therapeutic opportunity for many central nervous system (CNS) pathologies. However, the blood-brain barrier (BBB) poses a challenge for their delivery into the brain parenchyma. Nevertheless, numerous neurological diseases and brain pathologies, including cancer, result in BBB leakiness favoring single-domain antibodies uptake into the CNS. Some single-domain antibodies have been reported to naturally cross the BBB. In addition, different strategies and methods to deliver both nanobodies and VNARs into the brain parenchyma can be exploited when the BBB is intact. These include device-based and physicochemical disruption of the BBB, receptor and adsorptive-mediated transcytosis, somatic gene transfer, and the use of carriers/shuttles such as cell-penetrating peptides, liposomes, extracellular vesicles, and nanoparticles. Approaches based on single-domain antibodies are reaching the clinic for other diseases. Several tailoring methods can be followed to favor the transport of nanobodies and VNARs to the CNS, avoiding the limitations imposed by the BBB to fulfill their therapeutic, diagnostic, and theragnostic promises for the benefit of patients suffering from CNS pathologies.
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页数:23
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