One Responsive Stone, Three Birds: Mn(III)‐Hemoporfin Frameworks with Glutathione‐Enhanced Degradation, MRI, and Sonodynamic Therapy

Abstract

Ultrasound-driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep-seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)hemoporfin frameworks (Mn(III)-HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl-ether (HMME) to coordinate with Mn(III) ions. Mn(III)-HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)-HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d-electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost 1 O 2 generation ability under US irradiation. As a result, when Mn(III)-HFs/PEG dispersion is intravenously administered into mice, it exhibits high-contrast T 1 /T 2 dual-modal MRI and significant suppression for the growth rate of the deep-seated tumor. Furthermore, Mn(III)-HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)-HFs/PEG exhibit GSH-enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.

On-demand assembly of polymeric nanoparticles for longer-blood-circulation and disassembly in tumor for boosting sonodynamic therapy

“…Under 488 nm light excitation, the fluorescent spectrum of FITC-labeled-CAT@HA-HMME NPs ( Fig. S2d ) is featured with three emission peaks at 518, 613, and 674 nm, which are respectively indexed to FITC (518 nm) and HMME (613 and 674 nm) [ 36 ] characteristic peaks. Meanwhile, the encapsulation capability of CAT was determined by bicinchoninic acid (BCA) protein assay, and it is calculated to be 22.5% ( Fig.…”

Smart Manganese Dioxide-Based Lanthanide Nanoprobes for Triple-Negative Breast Cancer Precise Gene Synergistic Chemodynamic Therapy

“…In the TME, the nanoplatform not only acts as an siRNA delivery carrier to realize precise gene therapy but also mediates an excellent CDT effect for the generation of toxic • OH due to the Fenton-like effect of Mn 2+ produced by the degradation of MnO 2 . Intracellular GSH was depleted by MnO 2 to GSH disulfide (GSSG), which promoted the Fenton-like reaction and enhanced the generation of • OH (Figure A). , To investigate the • OH generation ability of the as-synthesized probes on tumor cells, we first designed experiments to evaluate their efficiency of generating Mn 2+ . Different concentrations of GSH solutions were mixed with the as-prepared ErNPs@MnO 2 -RGD solution (1 mmol L –1 of Mn) followed by inductively coupled plasma (ICP) mass spectrometry analysis of the supernatant to obtain a distribution map of Mn 2+ , which showed that Mn 2+ was generated with increasing concentrations of GSH (Figure B).…”

GSH-Sensitive Nanoscale Mn3+-Sealed Coordination Particles as Activatable Drug Delivery Systems for Synergistic Photodynamic-Chemo Therapy

“…MnCPs were prepared according to our previous report with Mn(OAc) 3 •2H 2 O (30 mg) and HMME (20 mg) as key components. 37 The obtained nanoparticles (MnCPs) were centrifuged and washed with ethyl alcohol and deionized water three times.…”