Harnessing Hydrogen-Bonded Organic Frameworks as Biosafe MRI Contrast Agents for Tumor Detection and Guided Surgery

Gadolinium (Gd)-based magnetic resonance imaging (MRI) contrast agents (CAs) suffer from limitations including rapid renal clearance and potential biological risks, highlighting the urgency to develop safer and more efficient alternatives. Herein, we report a novel Mn(II)-based MRI CA (Mn@nPFC-1) constructed by loading Mn 2+ ions into a nanoscale hydrogen-bonded organic framework (nPFC-1), which is self-assembled from 1,3,6,8-tetra( p -benzoic acid)pyrene (H 4 TBAPy). The Mn@nPFC-1 exhibits high stability benefiting from its integration of hydrogen bonding and π–π stacking interactions between the building blocks. In-vitro MRI tests under 3.0 T scanner show that Mn@nPFC-1 exhibits a high longitudinal relaxation rate ( r 1 = 7.40 mM –1 ·s –1 ), which is significantly superior to the clinically approved MnDPDP and clinical used Gd-based CAs. Fast field cycling nuclear magnetic resonance (FFC-NMR) reveals that the enhanced relaxation performance arises from the restricted rotational motion of Mn 2+ and the prolonged rotational correlation time. In-vivo studies across multiple tumor models demonstrate that Mn@nPFC-1 enables effective T 1 -weighted MRI contrast enhancement; it can further detect ultrasmall tumors (3.29 mm 3 ) and assist in accurate MRI-guided tumor resection. This work provides a promising strategy for designing biosafe, high-performance Mn-based MRI CAs using hydrogen-bonded organic frameworks as carriers, holding great potential for clinical tumor diagnosis and image-guided therapy.