International journal of nanomedicine · 2026
Synergistic Photothermal-Chemotherapy of Hepatocellular Carcinoma and Cancer Stem Cells via in situ pH-Responsive Hydrogels.
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Wu Yunchao, Xu Xin, Zhu Zhen, Du Fengyi, Zheng Guojun
Аннотация
PURPOSE: Monotherapy with photothermal therapy (PTT) hardly achieves durable and significant antitumor efficacy. To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thioridazine (THZ) was loaded into a gel network formed by the Schiff base cross-linking of amino-functionalized graphene quantum dots (NH2-GQDs) and oxidized dextran. A pH-responsive injectable carbon dot composite hydrogel delivery system (NTD@Gel) with dual effects of photothermal therapy and chemotherapy was thereby constructed.
METHODS: The techniques including HRTEM, XPS, FTIR, SEM and rheological tests were employed to verify the successful fabrication of NTD@Gel and characterize its physicochemical properties. In vitro and in vivo experiments were conducted to comprehensively evaluate the antitumor efficacy and biosafety of this hydrogel.
RESULTS: NTD@Gel exhibited excellent photothermal conversion performance and biocompatibility, and enabled the rapid and sustained release of THZ in the acidic microenvironment. In vitro experiments confirmed that NTD@Gel could synergistically kill Hep1-6 hepatocellular carcinoma cells through photothermal ablation and THZ-induced oxidative damage, and inhibited the oncogenic Akt/Stat3 signaling pathway activation. In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice.
CONCLUSION: NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy.
METHODS: The techniques including HRTEM, XPS, FTIR, SEM and rheological tests were employed to verify the successful fabrication of NTD@Gel and characterize its physicochemical properties. In vitro and in vivo experiments were conducted to comprehensively evaluate the antitumor efficacy and biosafety of this hydrogel.
RESULTS: NTD@Gel exhibited excellent photothermal conversion performance and biocompatibility, and enabled the rapid and sustained release of THZ in the acidic microenvironment. In vitro experiments confirmed that NTD@Gel could synergistically kill Hep1-6 hepatocellular carcinoma cells through photothermal ablation and THZ-induced oxidative damage, and inhibited the oncogenic Akt/Stat3 signaling pathway activation. In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice.
CONCLUSION: NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy.