Cisplatin And Imiquimod-Loaded Thermosensitive Gel Drug Delivery System Based On 2D MXene Nanosheet For Local Immuno-Chemotherapy Combined With Photothermal Therapy For Lung Cancer

Objective: The high incidence of lung cancer and the poor prognosis of traditional means such as surgery and radiotherapy requires exploring novel means of treating lung cancer.Although nanotherapeutic research has gained a lot of development,the disadvantages such as simple treatment and large side effects still need further improvement.To effectively treat lung cancer,we developed a temperature-sensitive hydrogel-based local injection therapeutic system with near-infrared triggered drug release.The system uses 2D MXene nanosheets with outstanding photothermal conversion ability as carriers loaded with R837 and cisplatin(DDP),which are subseq uently encapsulated into a temperature-sensitive hydrogel to constitute PEG-MXene@DDP@R837@SHDS(MDR@SHDS),followed by in situ injections of MDR@SHDS into tumor tissues combined with PTT.The immune adjuvant R837 ca n act as a phagocytic agent by promoting the maturation of dendritic cells(DCs)follo wed by phagocytosis of tumor cells.Photothermal therapy(PTT)induces apoptosis an d necrosis of tumor cells by converting light energy into heat energy.MDR@SHDS pr ovides synergistic anti-tumor treatment through a multi-modality approach of local im munotherapy,chemotherapy,and PTT,and avoids the low concentration of drug enric hment at the tumor site,bone marrow suppression,and immune-related adverse effects caused by systemic administration.Methods: Transmission electron microscopy(TEM),X-ray photoelectron spectroscopy(XPS),phase transition temperature,and near-infrared thermography were used to characterize the material properties,photothermal stability,and controlledrelease properties of MDR@SHDS.In the in vitro cell experiments,the proliferation,and apoptosis of Lewis cells were evaluated by CCK-8,Edu,and TUNEL.In in vivo animal experiments,Lewis tumor-bearing C57 mice transplanted tumors were used as a model to assess the photothermal effects at the tumor site using near-infrared thermography.The maturation of DCs and the ratio of CD4,and CD8 T immune cells in mice were assessed by flow cytometry.The in vivo anti-tumor effect of MDR@SHDS was verified by recording tumor growth change curves and staining tumor sections using HE and TUNEL.Results: The material characterization results show that the hydrogel has good temperature sensitivity,controlled release properties,and high biocompatibility.In vitro experiments showed that MDR@SHDS combined with the PTT group had a higher inhibitory effect on tumor cell proliferation than the MDR@SHD group alone.In Lewis transplanted tumors of C57 mice,MDR@SHDS showed good photothermal effects,while R837 released from MDR@SHDS induced more DCs to mature and exerted effective immune antitumor effects compared with the control group.The combination of local immunotherapy,chemotherapy,and PTT has better anti-tumor effects than local immunotherapy or chemotherapy alone.Conclusions:Thus,this study demonstrates that MDR@SHDS is simple to prepare,biocompatible,and a new potential therapeutic tool for the clinical treatment of lung cancer.