Mn₃O₄ Nanoshell Coated Metal–Organic Frameworks with Microenvironment‐Driven O₂ Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies

Abstract

Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn 3 O 4 @HA is created in a simple one-step process by coating Mn 3 O 4 nanoshells on the PCN-224 template, which can then be used as an "ROS activator" to exert catalase-and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn 2+ produced cytotoxic hydroxyl radicals (•OH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment (TME), Mn 3 O 4 nanoshells downregulated hypoxia-inducible factor 1𝜶 expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergistic PDT/CDT, and prevent tumor resurgence by remodeling TME.

Manganese(III) Phthalocyanine Complex Nanoparticle-Loaded Glucose Oxidase to Enhance Tumor Inhibition through Energy Metabolism and Macrophage Polarization

“…Taking into account the catalytic behavior of Mn­(III)-related materials, we investigated the catalytic potential of MnClPc–HSA@GOx NPs in generating ROS from H 2 O 2 . First, we tested the 1 O 2 generation using 9,10-anthracenediyl-bis­(methylene)­dimalonic acid (ABDA) as a probe.…”

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

“…Molecules 2024, 29, x FOR PEER REVIEW 6 of 14 to a strong four-line signal with a 1:2:2:1 peak-to-peak intensity pattern, characteristic of the generation of •OH from H2O2 [4,5]. Fe-TMPP is supported by a porphyrin-based ligand, which is often used for type II PDT of cancer [3,7,37].…”

“…Materials designed to target the unique features of the tumor microenvironment (TME), such as the over-expression of H 2 O 2 and glutathione (GSH), weak acidity, hypoxia, and immunosuppression, are attracting intensive interest in the field of nanomedicine [ 1 , 2 , 3 , 4 , 5 , 6 ]. Materials that are responsive exclusively to the TME imply low systemic toxicity and thus fewer side effects.…”

Polydopamine-Modified Zeolite Imidazole Framework Drug Delivery System for Photothermal Chemotherapy of Hepatocellular Carcinoma

“…As emerging class of hybrid porous materials constructed from metal nodes and organic linkers, metal organic frameworks (MOFs) gain numerous attentions in recent years and widely applicated in catalysis, gas separation and conversion, chemical sensors, and biomedicine. , With the intrinsic characteristics of large surface areas and highly ordered porosities, MOFs exhibit potent capability of loading and releasing different therapeutic cargoes. − Zeolitic imidazolate frameworks (ZIF-8) as a new porous material consist of zinc ions and 2-methylimidazole, which endow it with pH responsiveness, size controllable adjustment, and comparable compatibility. As an excellent drug carrier, cargoes can be easily encapsulated on the surface or center of ZIF-8 via multiple interactions such as electrostatic adsorption, coordination, and π–π stacking .…”