A Versatile G‐quadruplex (G4)‐coated Upconverted Metal‐Organic Framework for Hypoxic Tumor Therapy
Résumé
Given the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. One of the most efficient strategies combines several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Here, the G-quadruplex (G4)-forming sequence AS1411-A (d-(G2T)4TG(TG2)4A) was designed and used for its anti-tumor and biocatalytic properties, such as increasing the production of O2 ca. 2fold as compared to the parent AS1411 sequence. Subsequently, the AS1411-A/hemin complex (GH) was grafted on the surface and pores of a core-shell upconverted metalorganic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibited enhanced colloidal stability, increased targeting of tumor cells and improved O2 production (8.5-fold) in situ. When irradiated with near-infrared (NIR) light, the UMGH antitumor properties were bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1 O2). Combined with the antiproliferative activity of AS1411-A, this novel approach herein lays the foundation for a new type of G4-based nanomedicine.
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