Figure 6.

Bioinspired brain‐targeted delivery strategies. Immune cells can be used as a “trojan horse” for brain‐targeted delivery. Therapeutics can be either encapsulated in cells, conjugated to the cell surface or utilize “backpacks.” Conjugating LNPs with ligands of VCAM‐1 significantly increase accumulation in the inflamed brain endothelium. The anticancer drug PTX was first encapsulated into cationic liposomes (PTX‐CL), followed by merger with NEs to form PTX‐CL/NEs to migrate across the BBB and target inflamed brain where infiltrating tumor cells locate. cRGD liposomes co‐migrate with monocytes to cross BBB. Therapeutics containing “backpacks” attach to macrophages to cross the BBB. Alternatively, bispecific antibodies which target both brain endothelial cells and inflammatory cytokine in the brain parenchyma show potential to inhibit neuroinflammation. Chronic treatment with the cTfRMAb‐TNFR fusion protein, a BBB‐penetrating biologic TNF‐α inhibitors, offers therapeutic benefits by targeting neuroinflammation, leading to the restoration of BBB integrity.