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.

Photodynamic therapy( PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells.H owever,ahigh concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species.T oa ddress this problem, we report the development of ap hotosensitizer-MnO 2 nanosystem for highly efficient PDT.I no ur design, MnO 2 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.O nce endocytosed, the MnO 2 nanosheets are reduced by intracellular GSH. As ar esult, 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 MnO 2 nanosheets,c an provide af luorescence signal for monitoring the efficacy of delivery.Photodynamic therapy (PDT) is aclinical cancer treatment method which utilizes reactive oxygen species,such as singlet oxygen ( 1 O 2 )generated through the reaction between aphotosensitizer and tissue oxygen under illumination, to kill cancer cells.I nc omparison with traditional cancer therapy methods,s uch as surgery,c hemotherapy,a nd radiotherapy, PDT possesses several unique advantages,including minimal invasion, fewer side effects,n egligible drug resistance,a nd low minimal toxicity. [1][2][3] As ac onsequence,q uite af ew PDT agents (photosensitizers) that possess high 1 O 2 quantum yields with excellent photophysical properties and good biocompatibility have been discovered for cancer treatment. [4][5][6][7][8] In parallel, the search for strategies enabling efficient delivery of photosensitizers into cancer cells is ongoing. One efficient approach employs nanocarriers to deliver cancer treatment agents into cancer cells. [9][10][11][12][13][14][15] In the past two decades,d ifferent nanomaterials,s uch as metallic, carbon, silica, and organic polymer nanomaterials,have been developed for intracellular photosensitizer delivery. [16][17][18][19][20][21][22] Glutathione (GSH) is an important antioxidant and the most abundant low-molecular-weight thiol in vivo,w ith ac oncentration range from 1t o1 5mm.[23] At the same time, however, it has been shown to consume 1 O 2 generated by PDT agents,t hus greatly reducing the efficiencyo fP DT and limiting the clinical applications of current PDT agents. [24][25][26] Therefore,the development of amultifunctional nanosystem which can both enhance the cellular uptake of photosensitizers and decrease the level of GSH in cancer cells in situ is highly desired.MnO 2 nanosheets,w hich are ultrathin semiconductors, have attracted extensive attention in bioanalysis,cell imaging, and drug delivery.[27-31] They exhibit several unique features favorable for the delivery of photosensitizers with enhanced PDT efficiency. First, MnO 2 nanosheets can strongly adsorb small organic molecules,such...