Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron–hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS₂-Ti₃C₂ (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron–hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS₂-Ti₃C₂/TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.

Theranostic nanodrugs combining magnetic resonance imaging (MRI) and cancer therapy have attracted extensive interest in cancer diagnosis and treatment. Herein, a manganese (Mn)-doped mesoporous polydopamine (Mn-MPDA) nanodrug incorporating the nitric oxide (NO) prodrug BNN6 and immune agonist R848 was developed. The nanodrug responded to the H⁺ and glutathione being enriched in tumor microenvironment to release R848 and Mn²⁺. The abundant Mn²⁺ produced through a Fenton-like reaction enabled a highly sensitive T1-T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug, based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy. Meanwhile, R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype. Consequently, a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer, which manifested the great promise of this multifunctional nanoplatform in cancer treatment.