聚(I:C)包裹的 PLGA-PEI 纳米粒子用于个性化癌症免疫疗法。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-03-01 DOI:10.1007/s13346-024-01557-2
Lorena Gonzalez-Melero, Edorta Santos-Vizcaino, Ruben Varela-Calvino, Iria Gomez-Tourino, Aintzane Asumendi, Maria Dolores Boyano, Manoli Igartua, Rosa Maria Hernandez
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引用次数: 0

摘要

黑色素瘤是皮肤癌的主要致死原因,其发病率在全球范围内呈惊人的增长趋势。然而,传统疗法对晚期或转移性患者缺乏疗效。与此同时,免疫疗法已被证明是一种有效的治疗方法,但癌症患者的应答率仍远未达到理想状态。在这里,我们将患者提取的黑色素瘤新抗原封装在聚乙烯亚胺(PEI)功能化的聚(乳酸-共-乙醇酸)(PLGA)纳米粒子(NPs)中,并在其表面涂上聚肌苷酸:聚胞苷酸(poly(I:C)),从而开发出一种基于新抗原肽的个性化癌症疫苗。我们发现,PLGA NPs 可被有效改性,以包覆免疫佐剂聚(I:C),并包裹新抗原。此外,我们还发现树突状细胞(DC)和淋巴细胞都能受到有效刺激。此外,与不含聚(I:C)或不含抗原的 NP 相比,所开发的 NP 具有更好的免疫激活特性。我们的研究结果表明,所开发的疫苗具有很强的激活免疫系统的能力,能有效地使直流细胞成熟以呈现所选择的抗原,并促进淋巴细胞的活性以发挥其细胞毒性功能。因此,所产生的免疫反应是消除黑色素瘤肿瘤细胞的最佳和特异性免疫反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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PLGA-PEI nanoparticle covered with poly(I:C) for personalised cancer immunotherapy.

Melanoma is the main cause of death among skin cancers and its incidence worldwide has been experiencing an appalling increase. However, traditional treatments lack effectiveness in advanced or metastatic patients. Immunotherapy, meanwhile, has been shown to be an effective treatment option, but the rate of cancers responding remains far from ideal. Here we have developed a personalized neoantigen peptide-based cancer vaccine by encapsulating patient derived melanoma neoantigens in polyethylenimine (PEI)-functionalised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and coating them with polyinosinic:polycytidylic acid (poly(I:C)). We found that PLGA NPs can be effectively modified to be coated with the immunoadjuvant poly(I:C), as well as to encapsulate neoantigens. In addition, we found that both dendritic cells (DCs) and lymphocytes were effectively stimulated. Moreover, the developed NP was found to have a better immune activation profile than NP without poly(I:C) or without antigen. Our results demonstrate that the developed vaccine has a high capacity to activate the immune system, efficiently maturing DCs to present the antigen of choice and promoting the activity of lymphocytes to exert their cytotoxic function. Therefore, the immune response generated is optimal and specific for the elimination of melanoma tumour cells.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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