A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy

• Published in: Journal of inorganic biochemistry Vol. 241; p. 112133
• Main Authors: Zhang, Hai-Lin, Wang, Yi, Tang, Qi, Ren, Bing, Yang, Shi-Ping, Liu, Jin-Gang
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2023
• Subjects: Fenton-like reaction; Manganese dioxide; Nitric oxide delivery; Ruthenium nitrosyl; Synergistic therapy; Tumor microenvironment modulation; NO; AFIPB; Tumor microenvironment modulation; EDC; MRI; MTT; PDA; Manganese dioxide; PTT; CDT; H-MnO2; RDPP; MB; FTIR; Ruthenium nitrosyl; NHS; OH; XPS; CLSM; GSH; Synergistic therapy; PBS; DTNB; Nitric oxide delivery; TME; BET; NPs; DCFH-DA; NIR; ROS; Fenton-like reaction; FA; TEM
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2023.112133

A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn2+ further catalyzed the decomposition of endogenous H2O2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy. A novel mesoporous MnO2-based multifunctional nanoplatform exhibited near-infrared light-controlled nitric oxide delivery, tumor microenvironment (TME)-responsive release of a histone deacetylase inhibitor and TME modulation for efficient multimodal synergistic antitumor therapy. [Display omitted] •A hollow mesoporous MnO2-based multifunctional NO-releasing nanoplatform was prepared.•Tumor microenvironment-responsive of GSH depletion and hydroxyl radical production.•Controlled NO delivery and photothermal effect was achieved upon 808 nm light irradiation.•It showed high mortality toward cancer cells under 808 nm light irradiation.•Synergistic multimodal therapies were attributed to the enhanced antitumor efficiency.