Xiaoxia Han

MXenes, an emerging family of graphene-analogues two-dimensional (2D) materials, have attracted continuous and tremendous attention in many application fields because of their intrinsic physiochemical properties and high performance in versatile applications. In this work, we report on the construction of tantalum carbide (Ta4C3) MXene-based composite nanosheets for multiple imaging-guided photothermal tumor ablation, which has been achieved by rational choice of the composition of MXenes and their surface functionalization. A redox reaction was activated on the surface of tantalum carbide (Ta4C3) MXene for in situ growth of manganese oxide nanoparticles (MnOx/Ta4C3) based on the reducing surface of the nanosheets. The tantalum components of MnOx/Ta4C3 acted as the high-performance contrast agents for contrast-enhanced computed tomography, and the integrated MnOx component functionalized as the tumor microenvironment-responsive contrast agents for T1-weighted magnetic resonance imaging. The photothermal-conversion performance of MnOx/Ta4C3 composite nanosheets not only has achieved contrast-enhanced photoacoustic imaging, but also realized the significant tumor-growth suppression by photothermal hyperthermia. This work broadens the biomedical applications of MXenes, not only by the fabrication of family members of biocompatible MXenes, but also by the development of functionalization strategies of MXenes for cancer-theranostic applications.

The conventional inorganic semiconductors are not suitable for in vivo therapeutic nanomedicine because of the lack of an adequate and safe irradiation source to activate them. This work reports on the rational design of titania (TiO2)-based semiconductors for enhanced and synergistic sono-/photoinduced tumor eradication by creating an oxygen-deficient TiO2–x layer onto the surface of TiO2 nanocrystals, which can create a crystalline-disordered core/shell structure (TiO2@TiO2–x) with black color. As found in the lessons from traditional photocatalysis, such an oxygen-deficient TiO2–x layer with abundant oxygen defects facilitates and enhances the separation of electrons (e–) and holes (h+) from the energy-band structure upon external ultrasound irradiation, which can significantly improve the efficacy of sono-triggered sonocatalytic tumor therapy. Such an oxygen-deficient TiO2–x layer can also endow black titania nanoparticles with high photothermal-conversion efficiency (39.8%) at the NIR-II biowindow (1064 nm) for enhanced photothermal hyperthermia. Both in vitro cell level and systematic in vivo tumor-bearing mice xenograft evaluations have demonstrated the high synergistic efficacy of combined and enhanced sonodynamic therapy and photothermal ablation as assisted by oxygen-deficient black titania, which has achieved complete tumor eradication with high therapeutic biosafety and without obvious reoccurrence. This work not only provides the paradigm of high therapeutic efficacy of a combined sono-/photoinduced tumor-treatment protocol but also significantly broadens the nanomedical applications of semiconductor-based nanoplatforms by rational design of their nanostructures and control of their physiochemical properties.

Abstract Cancer recurrence after surgical resection (SR) is a considerable challenge, and the biological effect of SR on the tumor microenvironment (TME) that is pivotal in determining postsurgical treatment efficacy remains poorly understood. Here, with an experimental model, we demonstrate that the genomic landscape shaped by SR creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells, fostering cancer progression and hindering PD-L1 blockade therapy. To address this issue, we engineer a radio-immunostimulant nanomedicine (IPI549@HMP) capable of targeting myeloid cells, and catalyzing endogenous H 2 O 2 into O 2 to achieve hypoxia-relieved radiotherapy (RT). The enhanced RT-mediated immunogenic effect results in postsurgical TME reprogramming and increased susceptibility to anti-PD-L1 therapy, which can suppress/eradicate locally residual and distant tumors, and elicits strong immune memory effects to resist tumor rechallenge. Our radioimmunotherapy points to a simple and effective therapeutic intervention against postsurgical cancer recurrence and metastasis.

A theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique theranostic nanoplatform with multiple capabilities paves a new way toward personalized medicine by rational utilization.