Mn 3 O 4 Nanoshell Coated Metal-Organic Frameworks with Microenvironment-Driven O 2 Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies.

Nanomedicine has the emerging potential to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC), a subcategory of breast cancer with a high degree of malignancy. As a type of fascinating drug carrier, nanoscale metal-organic frameworks (NMOF) have attracted much attention in biomedical fields for effective tumor therapy due to their unique properties, including tumor microenvironment (TME) stimuli-responsiveness, promising catalytic activity, and high biocompatibility. Nevertheless, it is still difficult to develop a precise co-delivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 was 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 (PMH) was created in a simple one-step process by coating Mn 3 O 4 nanoshells on the PCN-224 template, which could then be used as a "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 TME, Mn 3 O 4 nanoshells down-regulated HIF-1α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multi-modality imaging abilities, can effectively inhibit tumor proliferation through PDT combined with CDT, and prevent tumor resurgence by remodeling TME. This article is protected by copyright. All rights reserved.