Antitumor immunity triggered by photothermal therapy and photodynamic therapy of a 2D MoS2 nanosheet-incorporated injectable polypeptide-engineered hydrogel combinated with chemotherapy for 4T1 breast tumor therapy

Abstract

A multifunctional PC₁₀A/DOX/MoS₂ hydrogel was designed and prepared for chemotherapy/photothermal therapy/photodynamic therapy of 4T1 tumor, and the immune responses triggered by photothermal and photodynamic effect of MoS₂ nanosheet in the hydrogel were also studied. Positively charged DOX and negatively charged PC₁₀A were loaded on the surface of MoS₂ nanosheet through layer-by-layer method to prepare hybrid PC₁₀A/DOX/MoS₂ nanoparticles. PC₁₀A/DOX/MoS₂ nanoparticles were dispersed in PC₁₀A hydrogel to prepare PC₁₀A/DOX/MoS₂ hydrogel. 2D MoS₂ nanosheet in the hydrogel was simultaneously utilized as photothermal agent and photodynamic agent for the generation of hyperthermia and reactive oxygen species, respectively. This PC₁₀A/DOX/MoS₂ hydrogel was injectable and possessed excellent biocompatibility. The results of in vivo tumor-bearing mice experiments showed that a remarkably enhance tumor inhibition was observed by the combination of chemo-photothermal-photodynamic therapy compared with photothermal therapy, photodynamic therapy, or chemotherapy alone. In addition, the results of in vivo therapy exhibited that the PC₁₀A/DOX/MoS₂ hydrogel with laser irradiation could activate antitumor immune effects to suppress the growth of primary 4T1 breast tumors and distal lung metastatic nodules. Therefore, these results demonstrated that the PC₁₀A/DOX/MoS₂ hydrogel was promising to be utilized in antitumor immunity therapy triggered by photothermal therapy and photodynamic therapy for malignant tumor.