Theranostic Mn-Porphyrin Metal–Organic Frameworks for Magnetic Resonance Imaging-Guided Nitric Oxide and Photothermal Synergistic Therapy

Abstract

Chemotherapy remains restricted by its toxic adverse effects and resistance to drugs. The treatment of nitric oxide (NO) combined with imaging-guided physical therapy is a promising alternative for clinical applications. Herein, we report nanoscale metal–organic framework (NMOF) systems to integrate magnetic resonance (MR) imaging, spatiotemporally controllable NO delivery, and photothermal therapy (PTT) as a new means of cancer theranostics. As a proof of concept, the NMOFs are prepared with biocompatible Zr4+ ions and Mn-porphyrin as a bridging ligand. By inserting paramagnetic Mn ions into porphyrin rings, Mn-porphyrin renders the NMOFs strong T1-weighted MR contrast capacity and high photothermal conversion for efficient PTT. S-Nitrosothiol (SNO) is conjugated to the surfaces of the NMOFs for heat-sensitive NO generation. Moreover, single near-infrared (NIR) light triggers the controllable NO release and PTT simultaneously for their efficient synergistic therapy with one-step operation. Upon intravenous injection, NMOF–SNO shows effective tumor accumulation as exposed by the MR images of the tumor-bearing mice. When exposed to the NIR laser, the tumors of mice injected with NMOF–SNO are completely inhibited, verifying the efficiency of NMOF–SNO. For the first time, Mn-porphyrin NMOFs are developed to be an effective theranostic system for MR imaging-guided controllable NO release and photothermal synergetic therapy under single NIR irradiation.