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细胞内生成的免疫金纳米颗粒用于肿瘤的组合光热治疗和免疫治疗。

Intracellularly Generated Immunological Gold Nanoparticles for Combinatorial Photothermal Therapy and Immunotherapy against Tumor.

出版信息

Nano Lett. 2019 Sep 11;19(9):6635-6646. doi: 10.1021/acs.nanolett.9b02903. Epub 2019 Aug 12.

Abstract

Gold nanoparticle (AuNP) has been widely used in cancer photothermal therapy (PTT) for ablating accessible tumor, while it is insufficient for inhibiting tumor metastasis and relapse in current stage. Here, we first developed a novel immunological AuNP through intracellular generation and exocytosis for combinatorial PTT and immunotherapy. Melanoma B16F10 cells were employed to generate AuNPs first and then shed nanoparticle trapped vesicles to extracellular environment with retained tumor antigens (AuNP@B16F10). By further introducing the nanoparticles into dendritic cells (DCs), DC-derived AuNPs (AuNP@DC) were generated with enhanced biosafety, which can induce hyperthermia and provoke antitumor immune responses. This immunological nanoplatform demonstrated efficient inhibition or even eradication of primary tumor, tumor metastasis, as well as tumor relapse, with significantly improved overall survival of mice. With our design, the intracellularly generated AuNPs with immunological property could act as an effective treatment modality for cancer.

摘要

金纳米颗粒(AuNP)已广泛用于消融可接近肿瘤的癌症光热治疗(PTT),但在现阶段,其抑制肿瘤转移和复发的效果还不够。在这里,我们首次通过细胞内生成和胞吐作用开发了一种新型免疫 AuNP,用于联合 PTT 和免疫治疗。使用黑色素瘤 B16F10 细胞首先生成 AuNPs,然后将纳米颗粒捕获的囊泡释放到细胞外环境中,保留肿瘤抗原(AuNP@B16F10)。通过进一步将纳米颗粒引入树突状细胞(DC)中,生成具有增强生物安全性的 DC 衍生 AuNPs(AuNP@DC),可诱导高热并引发抗肿瘤免疫反应。这种免疫纳米平台显示出对原发性肿瘤、肿瘤转移甚至肿瘤复发的有效抑制作用,甚至可以消除它们,显著提高了小鼠的总生存率。通过我们的设计,具有免疫特性的细胞内生成的 AuNPs 可以作为癌症的有效治疗方式。

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