Porous SiO2-Based Reactor with Self-Supply of O2 and H2O2 for Synergistic Photo-Thermal/Photodynamic Therapy

Abstract

Purpose: Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H₂O₂ supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO₂-SiO₂@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo.

Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO₂, and coated with dopamine. Then, MnO₂ was modified on the SiO₂. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups.

Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H₂O₂ in the GOD-mediated reaction. The generated sufficient H₂O₂ was catalyzed by MnO₂ and HGNs-Fc@Ce6 to produce O₂ and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect.

Conclusion: The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.

Keywords: hypoxia; nanomaterial; photo-thermal therapy; photodynamic therapy.