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PLGA-多糖纳米疫苗在结直肠癌中发挥治疗作用。

PLGA- Polysaccharide Nanovaccines Exert Therapeutic Effect in Colorectal Cancer.

机构信息

The First School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.

School of Inspection, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Sep 12;19:9437-9458. doi: 10.2147/IJN.S479334. eCollection 2024.

Abstract

BACKGROUND

Tumor vaccines have achieved remarkable progress in treating patients with various tumors in clinical studies. Nevertheless, extensive research has also revealed that tumor vaccines are not up to expectations for the treatment of solid tumors due to their low immunogenicity. Therefore, there is an urgent need to design a tumor vaccine that can stimulate a broad anti-tumor immune response.

METHODS

In this work, we developed a nanovaccine (NP-TCL@APS), which includes nanoparticles loaded with colorectal cancer tumor cell lysates (TCL) and Astragalus polysaccharides (APS) into poly (lactic-co-glycolic acid) to induce a robust innate immune response. The NP-TCL@APS was identified by transmission electron microscopy and Malvern laser particle size analyzer. The killing and immune activation effects of NP-TCL@APS were evaluated in vitro. Finally, safety and anti-tumor efficacy were evaluated in the colorectal cancer tumor-bearing mouse model.

RESULTS

We found that NP-TCL@APS was preferentially uptaken by DC and further promoted the activation of DC in vitro. Additionally, nanoparticles codelivery of TCL and APS enhanced the antigen-specific CD8 T cell response and suppressed the growth of tumors in mouse models with good biocompatibility.

CONCLUSION

We successfully prepared a nanovaccine termed NP-TCL@APS, which can promote the maturation of DC and induce strong responses by T lymphocytes to exert anti-tumor effects. The strategy proposed here is promising for generating a tumor vaccine and can be extended to various types of cancers.

摘要

背景

肿瘤疫苗在临床研究中已在治疗各种肿瘤患者方面取得了显著进展。然而,广泛的研究也表明,由于其免疫原性低,肿瘤疫苗在治疗实体瘤方面并不尽如人意。因此,迫切需要设计一种能够刺激广泛抗肿瘤免疫反应的肿瘤疫苗。

方法

在这项工作中,我们开发了一种纳米疫苗(NP-TCL@APS),它包括负载结直肠癌细胞裂解物(TCL)和黄芪多糖(APS)的纳米颗粒,装入聚(乳酸-共-乙醇酸)中,以诱导强大的固有免疫反应。NP-TCL@APS 通过透射电子显微镜和马尔文激光粒度分析仪进行鉴定。评估了 NP-TCL@APS 的体外杀伤和免疫激活作用。最后,在结直肠癌荷瘤小鼠模型中评估了安全性和抗肿瘤疗效。

结果

我们发现 NP-TCL@APS 优先被 DC 摄取,并进一步促进了 DC 的体外激活。此外,纳米颗粒共递送 TCL 和 APS 增强了抗原特异性 CD8 T 细胞反应,并抑制了肿瘤的生长,具有良好的生物相容性。

结论

我们成功制备了一种名为 NP-TCL@APS 的纳米疫苗,它可以促进 DC 的成熟,并通过 T 淋巴细胞诱导强烈的反应,发挥抗肿瘤作用。这里提出的策略有望产生肿瘤疫苗,并可扩展到各种类型的癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8293/11406540/99305da17898/IJN-19-9437-g0001.jpg

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