Injectable Liquid Metal- and Methotrexate-Loaded Microsphere for Cancer Chemophotothermal Synergistic Therapy

With inherent fluidity and prominent photothermal conversion efficiency, multifunctional liquid metals (LMs) have been increasingly explored for various biomedical applications, especially as cancer therapeutic materials. Here, a series of LM- and/or methotrexate (MTX)-loaded microspheres, which are prepared by chitosan (CS) and formaldehyde, are employed to realize cancer chemophotothermal synergistic therapy under near-infrared (NIR) laser irradiation. The size of these microspheres is controllable and adjustable, and the preparation process is rather convenient. The LM- and MTX-loaded microspheres (CS/LM/MTX microspheres) are in the size range of 6-80 μm and exhibit an excellent photothermal effect of LM droplets, and MTX release, and thereby efficient in the inhibition of 4T1 cancer cell growth in vitro and in vivo. Further, the CS/LM/MTX microspheres were applied to tumor-bearing mice with intratumoral injection. The CS/LM/MTX microspheres can raise the local temperature of tumors to 60 °C in 1 min under NIR laser irradiation. Combined with the drug release of MTX, these microspheres showed better antitumor efficiency in vivo. Moreover, these microspheres display low toxicity and good biocompatibility, which are significant for practices in vivo. Hence, the demonstrated LM- and/or MTX-loaded microspheres reveal their superiority for cancer chemophotothermal synergistic therapy with NIR laser irradiation.