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Glutathione‐Activatable and O 2 /Mn 2+ ‐Evolving Nanocomposite for Highly Efficient and Selective Photodynamic and Gene‐Silencing Dual Therapy
Author(s) -
He Dinggeng,
Hai Luo,
He Xing,
Yang Xue,
Li HungWing
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201704089
Subject(s) - photodynamic therapy , gene silencing , glutathione , reactive oxygen species , singlet oxygen , nanocarriers , materials science , cancer cell , in vivo , cancer research , biophysics , cancer , biochemistry , chemistry , biology , nanotechnology , oxygen , gene , nanoparticle , enzyme , genetics , organic chemistry
Photodynamic therapy (PDT) has been applied in cancer treatment by converting O 2 into reactive singlet oxygen ( 1 O 2 ) to kill cancer cells. However, the effectiveness of PDT is limited by the fact that tumor hypoxia causes an inadequate O 2 supply, and the overexpressed glutathione (GSH) in cancer cells consumes reactive oxygen species. Herein, a multifunctional hybrid system is developed for selective and highly efficient PDT as well as gene‐silencing therapy using a novel GSH‐activatable and O 2 /Mn 2+ ‐evolving nanocomposite (GAOME NC). This system consists of honeycomb MnO 2 (hMnO 2 ) nanocarrier loaded with catalase, Ce6, and DNAzyme with folate label, which can specifically deliver payloads into cancer cells. Once endocytosed, hMnO 2 carriers are reduced by the overexpressed GSH to Mn 2+ ions, resulting in the reduction of GSH level and disintegration of GAOME NC. The released catalases then trigger the breakdown of endogenous H 2 O 2 to generate O 2 , which is converted by the excited Ce6 into 1 O 2 . The self‐sufficiency of O 2 and consumption of GSH effectively enhance the PDT efficacy. Moreover, DNAzyme is freed for gene silencing in the presence of self‐generated Mn 2+ ions as cofactors. The rational synergy of enhanced PDT and gene‐silencing therapy remarkably improve the in vitro and in vivo therapeutic efficacy of cancers.