Department of Hepatobiliary Surgery, Xiang'an Hospital of Xiamen University, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361102, Fujian, China.
Cancer Research Center, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, Fujian, China.
ACS Nano. 2024 Sep 3;18(35):24219-24235. doi: 10.1021/acsnano.4c05657. Epub 2024 Aug 22.
Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly(lactic--glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.
纤维肉瘤是一种恶性间叶组织肿瘤,具有侵袭性强、复发率高的特点,预后较差。阿霉素类药物如多柔比星(DOX)是纤维肉瘤的一线化疗药物,但疗效往往不理想。最近,利用干扰素基因刺激物(STING)介导的固有免疫已成为癌症治疗的一种有希望的策略。将化疗与免疫调节剂结合应用于化疗免疫治疗中,显示出增强治疗效果的潜力。在这里,我们介绍了一种先进的树突状细胞(DC)纳米疫苗,cGAMP@PLGA@CRTM(GP@CRTM),与低剂量 DOX 联合使用,以增强纤维肉瘤的化疗免疫治疗。该纳米疫苗由聚(乳酸-乙醇酸)(PLGA)纳米颗粒组成,其核心是 STING 激动剂 2,3-cGAMP(cGAMP@PLGA,GP),外壳是高表达钙网蛋白(CRT)的纤维肉瘤细胞膜(CRTM)。在疫苗表面暴露 CRT 有助于招募 DC 并刺激摄取,从而有效地将 STING 激动剂和肿瘤抗原同时递送至 DC。这种双重递药方法能有效激活 DC 中的 STING 通路,引发持续的免疫刺激。同时,低剂量 DOX 减少了化疗相关的副作用,直接杀死一部分肿瘤细胞,并增加了肿瘤的免疫原性,从而进一步增强了免疫治疗效果。因此,这些发现表明 DC 纳米疫苗 GP@CRTM 作为化疗增强剂的潜力。低剂量 DOX 与 DC 纳米疫苗的协同联合是一种强大的化疗免疫治疗策略,可优化全身纤维肉瘤的治疗效果。
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