A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

Abstract

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of Glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.

Two‐Dimensional Metal Oxide Nanomaterials for Next‐Generation Rechargeable Batteries

“…[241][242][243] Among them, 2D nanosheets have attracted extensive interest for a number of applications, such as catalysis, [244][245][246] biomedical science, [247][248][249][250][251] and energy storage and conversion devices, especially supercapacitors and [236] Copyright 2014, Nature Publishing Group. There are several polymorphs for MnO 2 , including α, β, γ, and δ phases, which are composed of [MnO 6 ] octahedral basic units.…”

Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

“…[12] Recent studies have reported that smartly engineered nanoplatforms allow for efficient ROS production and specific cancer therapy by integrating iron-based nanoparticles and H 2 O 2 and collaborating with tumor microenvironment and external stimuli. [13] Although this concept is still in its infancy, non-photodynamic systems towards tipping the balance of ROS to induce cell death while excluding the need for external inputs have shown great promise for effective cancer therapy. [14] In fact, the delicate balance of intracellular ROS level in cancer cells make these cells depend heavily on antioxidant systems and vulnerable to further oxidative stress.…”

Tumor Microenvironment‐Triggered Supramolecular System as an In Situ Nanotheranostic Generator for Cancer Phototherapy

“…[15] Alternatively, they could be reduced into Mn 2+ with the production of O 2 via intracellular H 2 O 2 (Figure 2A and Figure S6B,C (Supporting Information)). [16] TEM data revealed that in GSH or H 2 O 2 the typical 2D sheet-like nanostructure of MnO 2 /DVDMS (Figure 2B) changed into nanoDVD-like irregular nanoparticles (PBS, pH 5.5) (Figure 2C,D and the Supporting Information) with an average hydrodynamic size of 197.2 nm (GSH) or 122.4 nm (H 2 O 2 ) (Figure 2E). Similarly, the zeta potential of MnO 2 /DVDMS + GSH or MnO 2 /DVDMS + H 2 O 2 /H + was higher than that of MnO 2 or MnO 2 /DVDMS (Figure 2F).…”

“…When the cells were treated with MnO 2 , DVDMS, and MnO 2 /DVDMS plus 630 mn laser irradiation, DVDMS and MnO 2 /DVDMS demonstrated significant cytotoxicity (Figure 3D,E and Figure S10C (Supporting Information)). MnO 2 /DVDMS exhibited more effective PDT/PTT killing of MCF-7 cells than DVDMS, presumably due to several advantages of the in situ self-assembly strategy: (i) MnO 2 /DVDMS could react with GSH in the MCF-7 cells, therefore the consumption of ROS by endogenous GSH was reduced; [16] (ii) MnO 2 /DVDMS could react with H 2 O 2 in the MCF-7 cells and downregulate the expression of hypoxia-inducible factor 1 α (HIF-1 α ) (Figure S10D, Supporting Information), ameliorating hypoxia and providing more O 2 for PDT; [17] (iii) after the release of Mn 2+ and DVDMS from the reduction of MnO 2 /DVDMS, nanoDVD was formed and both the efficacies of PDT and PTT were enhanced.…”