Dual and multi-targeted nanoparticles for site-specific brain drug delivery

In recent years, nanomedicines have emerged as a promising method for central nervous system drug delivery, enabling the drugs to overcome the blood-brain barrier and accumulate preferentially in the brain. Despite the current success of brain-targeted nanomedicines, limitations still exist in terms of the targeting specificity. Based on the molecular mechanism, the exact cell populations and subcellular organelles where the injury occurs and the drugs take effect have been increasingly accepted as a more specific target for the next generation of nanomedicines. Dual and multi-targeted nanoparticles integrate different targeting functionalities and have provided a paradigm for precisely delivering the drug to the pathological site inside the brain. The targeting process often involves the sequential or synchronized navigation of the targeting moieties, which allows highly controlled drug delivery compared to conventional targeting strategies. Herein, we focus on the up-to-date design of pathological site-specific nanoparticles for brain drug delivery, highlighting the dual and multi-targeting strategies that were employed and their impact on improving targeting specificity and therapeutic effects. Furthermore, the background discussion of the basic properties of a brain-targeted nanoparticle and the common lesion features classified by neurological pathology are systematically summarized.