MnO2-DNAzyme-photosensitizer nanocomposite with AIE characteristic for cell imaging and photodynamic-gene therapy

Abstract

Photodynamic therapy (PDT) was considered as an effective treatment. Whereas only PDT is not enough to achieve effective therapy on account of irradiation intensity decreases as depth increases as well as tumor hypoxia. Combination with gene therapy and photodynamic therapy have emerged as an effective strategy to improve therapeutic effectiveness. In the present study, a GSH responsive MnO₂ was employed to delivery TB and DNAzyme for cancer imaging and PDT-gene combination treatment. TB, a photosensiters with aggregation-induced emission characteristic, was employed for photodynamic therapy, while DNAzyme, acting as catalysts for the degradation of EGR-1 mRNA, was exploited for gene silencing. All of the results of tumor treatment in vitro have implied that MnO₂-DNAzyme-TB nanocomposite (MDT) can internalize into cells. Subsequently, MDT could decrease the expression of EGR-1 by gene silencing that enabling inhibition of cell growth. In addition, the singlet oxygen which was generated by the aggregated TB were able to further suppress cell growth. Combination therapy of photodynamic as well as gene therapy greatly enhanced antitumor efficiencies. Furthermore, in vivo tumor treatment experiments demonstrated that MDT under illumination can effectively inhibit the tumor growth of MCF-7 tumor-bearing mice by photodynamic and gene silencing combination therapy.

Keywords: Aggregation induced emission; DNAzyme; Gene silencing; MnO(2); Photodynamic therapy.