Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier

Abstract

Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer’s disease, stroke and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence, therapeutic potential, of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT targeting strategies have been developed over the past 20 years, and this review will explore exciting recent advances, with a particular emphasis on those studies showing brain targeting in vivo.

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…This result, together with the presence of a transferrin-mediated vesicle-based transcytosis system through the BBB [19,20,48,49] makes HFt-based NCs potentially good carriers for toxic molecules to the brain tumors.…”

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

“…73,74 Although actively targeted brain drug delivery has improved the crossing of nanoparticles into the brain, additional properties can be included in liposomal systems to enhance the delivery of drugs at the targeted site in response to specific stimuli, such as variations in temperature, magnetic field, ultrasound intensity, or changes in pH. For example, recent reports introduced the concept of magnetic liposomes as a targeting moiety for delivering of therapeutic molecules …”

Dendrimer-based magnetic resonance imaging agents for brain cancer

“…9c), thereby achieving higher delivery efficacy while sparing other cells to reduce toxicity. Different targeting agents such as antibodies, peptides and small molecular ligands have been applied to construct active targeting systems for tumor homing [84][85][86]. These systems can be further developed to create nanoplatforms for brain tumor targeting.…”

“…In order to achieve brain tumor targeting, researchers have used specific functional entities to overcome the BBB and actively target cancer cells [84,85,87]. It is expected that dendrimer-based imaging agents would accumulate and be enriched at the tumor lesions via the EPR effect and/or receptor-mediated transcytosis, then bind to ligands or receptors present on the brain cancer cell surface (Fig.…”