Work

Padlock-designed MOFs triggers an “avalanche effect” to enhance apoptosis and suppress metastasis in central nervous system lymphoma

Year: 2025

Type: article

Abstract: The increasing incidence of central nervous system lymphoma (CNSL) is hindered by the blood-brain barrier and costly prolonged drug development. To overcome these obstacles, we developed a carboplatin lock-designed MOF (Pt-MOFs@Glu) targeting intestinal macrophages for brain-directed drug transport. Single-cell RNA sequencing analyses revealed that intestinal macrophages migrate to the brain in response to chemokines. Building on this insight, Pt-MOFs@Glu was designed to engage these cells for precise delivery. Comprising carboplatin, pyrazine-quinoxaline, and β-glucan, the system induces an "avalanche effect" in the CNSL microenvironment, promoting tumor apoptosis and inhibiting metastasis. Combining pyrazine-quinoxaline to lock carboplatin and β-glucan to boost targeting, immunity, and oral absorption, the system enables ROS-triggered drug release, efficiently crosses the gastrointestinal tract and BBB, and synergizes chemo-immunotherapy to enhance therapeutic efficacy. This approach redefines CNSL treatment by harnessing the gut-brain axis, offering a transformative pathway to overcoming therapeutic barriers and improving patient outcomes.

Source: Science Advances

DOI: 10.1126/sciadv.adv2647