Reactive oxygen species (ROS) with strong oxidizing and high activity have been regarded as an effective "weapon" for antitumor therapy, since it can induce organelle injury, oxidative damage, and cell death. Herein, hollow structured manganese carbonate (MnCO3) nanocubes are fabricated and loaded with photosensitizer (chlorin e6, Ce6), obtaining a responsive nanoplatform H-MnCO3/Ce6-PEG (HMCP NCs). Two different approaches to upregulate intracellular ROS level were realized by HMCP NCs. On one hand, with irradiation of external laser, Ce6 could generate singlet oxygen (O-1(2)) through a multistep photochemical process applied in photodynamic therapy (PDT). On the other hand, MnCO3 could be specifically degraded into Mn2+ in an acidic tumor microenvironment (TME), triggering Mn2+-activated Fenton-like reaction to convert endogenous H2O2 into hydroxyl radical (center dot OH). In vitro combined chemodynamic therapy (CDT) and PDT showed that the metal ion-enhanced ROS production could break the intracellular redox equilibrium, thus leading to cell death. In vivo combined CDT/PDT with HMCP NCs exhibited remarkably enhanced therapeutic efficacy in inhibiting tumor growth, without resulting in noticeable damage to normal tissues. This work presents a unique type of manganese-based nanoplatform for efficiently generating ROS in solid tumors, favorable for ROS-involved therapeutic strategies.
[1]Nanjing Tech Univ NanjingTech, Key Lab Flexible Elect KLOFE, 30 South Puzhu Rd, Nanjing 211800, Jiangsu, Peoples R China.
[2]Nanjing Tech Univ NanjingTech, IAM, 30 South Puzhu Rd, Nanjing 211800, Jiangsu, Peoples R China.
[3]Liaocheng Univ, Sch Phys Sci & Informat Technol, Liaocheng 252059, Shandong, Peoples R China.
[4]Nanjing Univ Informat Sci & Technol, Sch Chem & Mat Sci, Nanjing 210044, Jiangsu, Peoples R China.
[5]Yuhuangding Hosp, Dept Chemotherapy, Yantai 264000, Shandong, Peoples R China.
(8.0+极速模式)