Exosomes/MoS2 complex for targeting and effective photothermal therapy

Photothermal therapy (PTT) has been an attractive tumor treatment strategy in recent years. Two-dimensional molybdenum disulfide (MoS₂)-based nanomaterials with high photothermal efficiency is a critical candidate for PTT. However, the tumor-targeting capability extremely needs to be improved for effective tumor treatment. In this work, we combine the MoS₂ nanodots with exosomes, native vesicles secreted from living cells, to construct a novel exosomes/MoS₂ complex (MoS₂@ME) for effective tumor-targeted PTT. Through ultrasonic self-assembly membranes, MoS₂ nanodots are incorporated into MCF-7 exosomes. Similar to free MoS₂, MoS₂@ME shows significant photothermal conversion effect, causing nearly 100% necrosis proportion of MCF-7 and 4T1 cells under 1064 nm laser irradiation within 5 min (0.4 W/cm²) in vitro. In particular, MoS₂@ME presents noteworthy affinity for tumor cells, and in vivo studies further prove that it could accumulate at the tumor site efficiently. After intravenous injection with MoS₂@ME plus NIR irradiation, the temperature of tumor site in 4T1 tumor-bearing mice could reach 46°C within a short time (~ 2 min). Notably, with the prolongation of NIR irradiation time, the temperature of tumors gradually increases and reaches the maximum temperature (52.3°C) at 8 min, which is far higher than that in the free MoS₂ group. More importantly, PTT using MoS₂@ME exhibits much more effective antitumor therapy, as the tumor volume and tumor weight of mice in the MoS₂@ME group are significantly lower than those in the PBS and MoS₂ groups (P < 0.05), and even the tumor disappears completely. In vitro and in vivo studies demonstrate that the MoS₂@ME shows excellent targeting capacity and photothermal effect, achieving effective photothermal cancer therapy. This work is expected to overcome the shortcomings of some photothermal materials, aiming to improve safety and effectiveness. The exosome-incorporated design strategy may pave a new way for molybdenum-based tumor-targeted PTT.