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一种用于高安全性和高效癌症光热联合免疫治疗的可靠 CpG 纳米平台。

A trustworthy CpG nanoplatform for highly safe and efficient cancer photothermal combined immunotherapy.

机构信息

State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials and Engineering, Research Center for Nano-Preparation Technology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.

出版信息

Nanoscale. 2020 Feb 14;12(6):3916-3930. doi: 10.1039/c9nr09402d. Epub 2020 Jan 31.

Abstract

Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.

摘要

钯纳米片(Pd NSs)由于其优异的近红外吸收、光热转换能力和生物相容性,最近在生物医学领域引起了越来越多的研究兴趣。然而,Pd NSs 在免疫治疗中的应用尚未见报道。在这里,Pd NSs 被用作免疫佐剂 CpG ODN 的载体,不仅可以有效地递送 CpG,还可以通过基于 Pd NS 的光热疗法(PTT)增强 CpG 的免疫治疗效果。Pd NSs 对免疫系统没有影响,所制备的 Pd-CpG 纳米复合材料,特别是 Pd(5)-CpG(PS),可以显著增加免疫细胞对 CpG 的摄取,并增强 CpG 在体外和体内的免疫刺激活性。通过 Pd(5)-CpG(PS)介导的 PTT 和免疫治疗的联合,实现了高效的肿瘤抑制,并且肿瘤荷瘤小鼠的存活率大大提高,这得益于安全的近红外(NIR)照射(808nm 激光,0.15W/cm)下的 Pd(5)-CpG(PS)。重要的是,联合治疗诱导肿瘤细胞死亡并释放肿瘤相关抗原,这些抗原可以在 CpG 的协助下被抗原呈递细胞有效摄取和呈递,从而导致 TNF-α 和 IL-6 的产生增加和细胞毒性 T 淋巴细胞(CTL)活性增强。这项工作为利用光热纳米材料进行安全高效的癌症光热联合免疫治疗提供了新的范例。

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