Traditional cancer treatments include surgery, radiation therapy, and chemotherapy; however, they have evident side effects. On the contrary, photothermal therapy has attracted considerable attention because of its non-invasive properties, precision, and lower side effects. Photothermal therapy is a treatment method in which a material with high photothermal conversion efficiency is injected into the biological body, and the material converts laser energy into heat energy to kill cancer cells under the irradiation of an external laser source. However, cells in hot environments initiate self-protection measures to resist the damage caused by high temperatures. To optimize the effect of photothermal therapy, a two-dimensional Ti₃C₂(MXene)-based nano reagent for synergistic photothermal chemotherapy was constructed, quercetin was selected as an anticancer drug, and the inhibitory effect of the nano reagent on tumor cells was explored at the cellular level.

In this study, LiF/HCl was used to selectively etch the Al layer of Ti₃AlC₂ to obtain accordion-like multilayer Ti₃C₂. The obtained wet precipitate was then dissolved in 40 mL of ethanol, sonicated for 80 min to cause initial stratification of the aggregates, washed repeatedly, and thereafter dissolved in deionized water. Finally, the supernatant was obtained as a nanosheet colloidal dispersion by centrifugation and purification after sonication in an ultrasonic cell crusher. Subsequently, the nanosheet surface was modified with the positively charged polymer polypropylene amine hydrochloride to make it positively charged, and PVP-modified quercetin was compounded onto the nanosheet by electrostatic adsorption to form a nanoreagent for synergistic photothermal/chemotherapy treatment. Next, the surface morphology was observed using transmission electron microscopy (TEM), and the composite was analyzed using Zeta potential analysis and absorption spectroscopy. The photothermal effects of the nanosheets and their complexes were subsequently evaluated, and the antitumor effects of this synergistic therapeutic nanoagent were evaluated in cells.

The prepared nanosheets are suitable in size, between about 200-300 nm, and applicable in biomedicine. It can also be observed that quercetin was successfully compounded onto the nanosheets [Fig. 2(c)]. By testing the Zeta potential of the PAH-modified MXene, PVP-modified quercetin, and the final compound, it can be visually confirmed that the final compound has a slightly decreased potential compared to the modified MXene. This indicates that quercetin was successfully complexed to the nanosheet surface [Fig. 2(d)]. Next, the absorption spectra of MXene, quercetin, and MXene@Qu were tested separately, and it was observed that the absorption peak at 261 nm is characteristic to quercetin, and the absorption window of MXene near the NIR appeared in the absorption spectrum of MXene@Qu. This further indicates that the MXene and quercetin were successfully compounded [Fig. 2(e)]. The UV-Vis-NIR absorption spectra revealed the relationship between the absorbance intensity of aqueous Ti₃C₂ nanosheets and the concentration of the material, which showed the concentration dependence of the absorbance of the composites in the first biological window [Fig. 2(f)]. The extinction coefficient α of the aqueous Ti₃C₂ nanosheets was calculated to be 24.05 L/(g·cm) according to the Lambert-Beer law, indicating that the prepared Ti₃C₂ has good near-infrared absorption properties. Subsequently, the concentration and excitation power were changed to observe the concentration- and power-dependent photothermal effects of the nanosheets, indicating that the photothermal effects can be fine-tuned by adjusting the nanosheet concentration or laser intensity. MXene@Qu exhibited good photothermal stability in subsequent heating and cooling cycles. The photothermal conversion efficiency of this nanosheet, obtained by quantitative calculation through one heating-cooling cycle to be 31.34% (Fig. 3). Then, via MTT cytotoxicity assay, it was found that more than 78.91% of the cells of this nanoreagent were killed by laser irradiation, which has a good anti-tumor effect (Fig. 4). In addition, the highest number of dead cells in the MXene@Qu+laser group was qualitatively observed in the live–dead cell staining (Fig. 5).The nanoreagent has excellent anti-tumor effects and achieves good therapeutic results in the in vivo cellular assays, leading to 78.91% cell death. In the future experiments, we will continue to explore the synergistic therapeutic effect of this nanoagent and construct HepG2 tumor-bearing nude mice to explore the effect of photothermal treatment in vivo to achieve the expected effect and effectively improve the efficiency of photothermal treatment.

In this study, we constructed a two-dimensional Ti₃C₂ (MXene)-based nanoreagent for synergistic photothermal chemotherapy treatment and described the therapeutic effects of the photothermal platform in terms of material properties, in vitro photothermal effects, and intracellular photothermal therapeutic effects. Compared with other photothermal agents, this nanoagent has a high conversion effect (31.34%), good photothermal stability, suitable size, and good hydrophilicity, all of which are in line with the requirements of nanobiotechnology.