Asymmetric Mesoporous Nanoformulation for Combination Treatment of Soft Tissue Sarcoma

Abstract

Soft tissue sarcoma (STS) is a kind of tumor that is difficult to treat by chemotherapy alone. In recent years, various studies have been conducted on the use of multifunctional nanoparticles with core@shell or indiscriminate coassembly to improve therapeutic efficacy. However, in these multifunctional nanoformulations, the functional subunits are located in the relevant space, in which the different functions are difficult to perform independently during the combination therapy. Herein, the enwinding-structured asymmetric mesoporous Fe3O4&mSiO2–SRF nanoformulation (SRF = Sorafenib) is constructed for the combination therapy of STS, in which the one-dimensional mSiO2 nanorods are enwound on the surface of magnetic Fe3O4 nanoparticles. In this enwinding-structured asymmetric nanoformulation, a Fe3O4 nanosphere subunit is used for the chemodynamic therapy (CDT), and a mesoporous SiO2 (mSiO2) subunit with high surface area is used for the loading of SRF chemotherapy drugs (mSiO2–SRF). Taking advantage of the spatial isolation of mSiO2–SRF and Fe3O4 subunits, the direct exposure of the Fe3O4 subunit can not only enhance the Fenton reaction on the nanoparticles surface but also accelerate the release of Fe2+/Fe3+ in the acidic microenvironment of the tumor, which further induced the upgrade of the cell oxidation level through GSH consumption and CDT. In addition, the SRF loaded mSiO2 functional unit can inhibit the synthesis of GSH, and synergistically work with the Fe3O4 functional unit to enhance the ferroptosis of cancer cells. Compared with traditional core@shell structured nanoformulation, the cancer cell killing efficiency of the asymmetric mesoporous nanoformulation is greatly increased by 41.33%, thus realizing improved tumor restrain efficiency in STS treatment.