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.

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer

“…When referring to PTT effect, clinicians have pointed out that tumor cells might occur apoptosis under 43–45 °C, while normal cells are generally tolerant to this temperature condition [ 36 ]. In another word, PTT effect refers to generating external 45 °C heating at cancer region, which is supposed to have a direct cytotoxic effect on tumor cells, and enhance the efficacy of chemotherapy and radiotherapy, improve the body’s immunity, and thus suppress tumor progression [ 18 , 37 ]. Coincidentally, it could be observed by the IR camera that when HGC-27 cells were treated with HMON@CuS/Gd (50 µg/mL) plus NIR irradiation (0.8 W/cm 2 , 5 min), the temperature could raise up to around 45 °C at 37 °C temperature condition.…”

MoS2-based nanocomposites for cancer diagnosis and therapy

“…18 ). Phototherapy could trigger body's immune response to improve the effectiveness of cancer therapies [ 259 , [375] , [376] , [377] ]. Cancer cells were destroyed by phototherapy and then released tumor associated antigens which can be captured by antigen presenting cells (particularly dendritic cells, DCs) and presented to T cells, subsequently inducing immune reactions to kills tumor cells.…”

“…Cancer cells were destroyed by phototherapy and then released tumor associated antigens which can be captured by antigen presenting cells (particularly dendritic cells, DCs) and presented to T cells, subsequently inducing immune reactions to kills tumor cells. Jin et al [ 377 ] synthesized an injectable PC 10 A/DOX/MoS 2 hydrogel that could be used for chemotherapy, phototherapy and immunotherapy of 4T1 tumor. MoS 2 nanosheet loaded with positively charged DOX and negatively charged PC 10 A to form hybrid PC 10 A/DOX/MoS 2 nanoparticles by electrostatic interaction and then dispersed them in PC 10 A hydrogel to prepare the multifunctional PC 10 A/DOX/MoS 2 hydrogel.…”

Drug Delivery Based on Stimuli-Responsive Injectable Hydrogels for Breast Cancer Therapy: A Review

“…An increasing number of research works show great interest in the application of combinational therapies to realize an enhanced therapeutic efficacy. Two or more therapeutic strategies are integrated into one smart hydrogel system to exert cancer-killing effects [ 9 , 11 , 35 ]. Some exciting achievements include combined photothermal and photodynamic therapy [ 11 , 24 ], combined photothermal and chemotherapy [ 63 ], or combined photothermal and immunotherapy [ 18 ].…”

“…All of these have positive effects on killing cancer cells [ 9 ]. Gold nanoparticles [ 64 ], indocyanine green [ 65 ], reduced graphene oxide [ 66 ], iron-oxide [ 67 , 68 ], MoS 2 [ 35 ], CuS [ 69 ], and black phosphorus quantum dots [ 36 ] have been reported as photo-responsive agents.…”