Recent advances in self-assembled nanoplatforms for central nervous system disorders therapy: Design principles, multifunctional strategies, and therapeutic applications.

The incidence of central nervous system (CNS) disorders is increasing worldwide, while the development of CNS drugs remains extremely challenging due to high costs, long development cycles, and high failure rates. The CNS is highly protected by physiological barriers, particularly the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), which severely restrict the entry of most therapeutic agents. Self-assembled nanocarriers (SA-NCs), characterized by relatively simple component composition and straightforward preparation processes, can be rationally engineered to bypass or penetrate these barriers, thereby enabling controlled and targeted drug delivery to the CNS. This review systematically summarizes recent advances in self-assembled nanoplatforms for CNS therapy. It first introduces the anatomical and functional barriers of the CNS along with current routes of administration. Subsequently, it explains the basic design principles and mechanisms of molecular self-assembly (SA), highlighting its unique advantages. The review then examines the multifunctional strategies of SA-NCs from the perspective of a spatiotemporal delivery process. Particular emphasis is placed on their ability to cross the BBB through membrane-translocating modifications for enhanced penetration, and subsequently accumulate at disease sites via functional modifications for targeted therapy. Finally, we discuss recent therapeutic applications in various CNS disorders and provide critical insights into current challenges in clinical translation, offering guidance for the future development of self-assembled nanomedicines.