Glioma microenvironment contains numerous myeloid cells, including brain-resident microglia and recruited monocytes and macrophages (Mo/Mφ). When studied collectively, these cells presented pro-tumor effects. Yet, little is known about the differences among these myeloid populations. Using single-cell sequencing analysis, we studied the phenotypic characteristics, spatial variances, and dynamic changes of these relatively heterogeneous cell populations. Microglia populations with distinct spatial distribution presented different functional states, including tumor-associated subsets with phagocytic and lipid metabolism signature. Notably, this subset of glioma-associated microglia shared similar trait in a diverse spectrum of neuropathogenesis. In contrast, Mo/Mφ highly expressed genes related to angiogenesis, tumor invasion, and immune evasion. Moreover, identifying the Mo/Mφ subsets had prognostic and classificatory value in clinical application. These results thus eliminate the long-existing ambiguity about the role of microglia and Mo/Mφ in glioma pathogenesis, and reveal their prognostic and therapeutic value for glioma patients.

At present, therapeutics for the diseases of central nervous system (CNS) are complicated by the presence of the blood-brain barrier (BBB). The BBB maintains intracranial homeostasis and facilitates brain-body communications, but hinders the effectiveness of drug-delivery systems based on nanoparticles (NPs). Great efforts have been devoted to the imprvement of NP-based brain delivery over the past decades. In addition to chemical modifications, biomimetic technologies such as cell membranes or neurotropic viruses camouflage, immune cells or extracellular vesicles (EVs) loading are promising candidates to make NPs ideal vehicles. This review summarizes the characteristics and transport mechanisms of BBB, and the recent advances in biomimetic technologies as well as administration methods that enhance the BBB penetration and targeting capabilities of NPs.