Developing therapeutic methods for central nervous system (CNS) diseases has been attracted attentions for the purpose of extending healthy life expectancy in this aging society. Blood-brain barrier (BBB), which consists of tight junction of brain capillary endothelial cells (BCECs) and astrocytic end-feet, prevents drugs from penetrating to the brain. Numerous researchers have been developed drug delivery strategies providing improved penetrating efficiency to therapeutic pharmaceutical agents. Among them, strategies utilizing nanoparticles (NPs) have been intensively studied as non-invasive delivery however NP-based CNS therapeutic application has not been launched yet.
In order to obtain comprehensive structural parameters of NPs for efficient drug delivery to the brain, we clarified the effect of charge ratio, ligand density, and mobility of ligand molecules of glucose-modified polyion complex (PIC) polymeric micelles on the efficiency of BBB penetration mediated by glucose transporters [1]. Meanwhile, it has been also suggested that the size of NP is another important parameter for the efficient drug delivery to the brain. For the purpose of investigating size effect on the performance of NPs, we developed facile and wide-range (30-200 nm) size tunable synthetic method of multi-color conjugated polymer NPs (Pdots) as a fluorescent probe [2]. The investigation of size effect on BBB permeability of NPs is expected to be visualized by multi-color size tunable Pdots.
Addition to synthetic NPs, biologically derived NPs have been widely studied not only for delivering drugs to the brain but also for pathological studies of CNS diseases. For example, bacterial extracellular vesicles (BEVs) transferred to the brain have been suggested to play a key role in the brain-gut axis, interaction between CNS and gut microbiota. Herein, the novel strategy to analyze biodistribution of BEVs based on gold NP labeling is proposed. We believe that clarifying the characteristics of BBB permeable BEVs determined by the origin of bacterial cells, the production mechanism, and the state of bacterial cells is expected to reveal mechanism of brain-gut axis and related pathology of CNS diseases.
References
[1] N. Nakamura, Y. Mochida, K. Toh, S. Fukushima, H. Cabral, Y. Anraku, Polymers 2020, 13 (1), 5.
[2] N. Nakamura, N. Tanaka, S. Ohta, RSC Adv. 2022, 12 (19), 11606-11611.