■灌注不足,经常由异常的血管结构引起,引起肿瘤缺氧。这种情况的存在阻碍了治疗药物的有效递送和免疫细胞渗入肿瘤,从而损害了对肿瘤的治疗效果。这项研究的目的是利用超声(US)的热效应,以诱导肿瘤内的局部温度升高,从而促进血管舒张,增强药物输送,增强免疫细胞浸润。
■US参数的选择基于肿瘤内温度升高及其对细胞活力的影响。使用酶联免疫吸附测定(ELISA)和免疫荧光检查研究了血管舒张和缺氧的改善。通过冰冻切片分析,分析了市售聚乙二醇化脂质体多柔比星(PLD)和PD-L1抗体(抗PD-L1)在肿瘤中的分布和积累,ELISA,和体内荧光成像。采用流式细胞术(FCM)对肿瘤免疫微环境进行评价。通过监测各种治疗后的肿瘤生长和生存率,研究了US增强化疗与免疫治疗相结合的疗效。
■美国0.8W/cm2照射条件10分钟有效地将肿瘤温度升高到大约40°C,而不会引起任何细胞或组织损伤,并充分诱导血管舒张,从而增强PLD和抗PD-L1在US治疗的肿瘤中的分布和递送。此外,它有效缓解肿瘤缺氧,同时显着增加M1表型肿瘤相关巨噬细胞(TAMs)和CD8T细胞,以及减少M2表型TAMs。通过结合美国照射,PLD和抗PD-L1的治疗效果显著提高,导致有效抑制肿瘤生长和延长小鼠生存期。
■应用US(0.8W/cm210分钟)可有效诱导血管舒张并增强PLD和抗PD-L1向肿瘤的递送,从而重塑免疫抑制肿瘤微环境并优化治疗结果。
UNASSIGNED: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration.
UNASSIGNED: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments.
UNASSIGNED: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice.
UNASSIGNED: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.