Asymmetric Mesoporous Nanoformulation for Combination Treatment of Soft Tissue Sarcoma

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 Fe 3 O 4 &mSiO 2 –SRF nanoformulation (SRF = Sorafenib) is constructed for the combination therapy of STS, in which the one-dimensional mSiO 2 nanorods are enwound on the surface of magnetic Fe 3 O 4 nanoparticles. In this enwinding-structured asymmetric nanoformulation, a Fe 3 O 4 nanosphere subunit is used for the chemodynamic therapy (CDT), and a mesoporous SiO 2 (mSiO 2 ) subunit with high surface area is used for the loading of SRF chemotherapy drugs (mSiO 2 –SRF). Taking advantage of the spatial isolation of mSiO 2 –SRF and Fe 3 O 4 subunits, the direct exposure of the Fe 3 O 4 subunit can not only enhance the Fenton reaction on the nanoparticles surface but also accelerate the release of Fe 2+ /Fe 3+ 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 mSiO 2 functional unit can inhibit the synthesis of GSH, and synergistically work with the Fe 3 O 4 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.