阳离子聚苯乙烯乳胶纳米载体用于向卵巢癌细胞递送免疫刺激长双链 RNA

IF 3.2 4区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of biomedical materials research. Part B, Applied biomaterials Pub Date : 2024-09-25 DOI:10.1002/jbm.b.35487
N. L. Aldor, N. A. Jadaa, S. Y. Miller, I. Alla, S. Richardson, V. Kitaev, S. J. Poynter
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引用次数: 0

摘要

长双链(ds)RNA 是 I 型干扰素和先天性免疫反应的有效刺激物。在本研究中,我们首次证明了阳离子聚苯乙烯胶乳纳米结构(clNPs)作为dsRNA载体的功效,它改善了细胞递送,并在卵巢癌细胞系SKOV3中有力地增强了dsRNA的免疫刺激能力。clNPs与体外转录的dsRNA分子复合物被SKOV3细胞结合,与未复合物clNPs相比,clNPs与dsRNA复合物的细胞结合率更高。两种干扰素刺激基因的转录表达量分别比 dsRNA 增加了 47 倍和 108 倍,并诱导了针对水泡性口炎病毒的显著抗病毒状态,使 dsRNA 的功效提高了 3.3 倍。这些数据凸显了聚苯乙烯胶乳纳米结构作为dsRNA载体用于抗癌免疫疗法的潜力,提高了核酸的吸收和疗效。
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Cationic Polystyrene Latex Nanocarriers for Immunostimulatory Long Double-Stranded RNA Delivery to Ovarian Cancer Cells

Long double-stranded (ds)RNA, a potent stimulator of type I interferon and the innate immune response. In the present study, we demonstrated, for the first time, the efficacy of cationic polystyrene latex nanostructures (clNPs) as a dsRNA carrier, improving cellular delivery and robustly potentiating the immunostimulatory capacity of dsRNA in the ovarian cancer cell line SKOV3. The clNPs complexed with an in vitro transcribed dsRNA molecule, were bound by SKOV3 cells, and had increased cellular association compared to uncomplexed clNPs. clNPs complexed with dsRNA induced a more robust innate immune response compared to dsRNA alone. Transcript expression of two interferon-stimulated genes, were increased 47- and 108-fold over dsRNA and induced a significant antiviral state against vesicular-stomatitis virus, resulting in a 3.3-fold improvement on the efficacy of dsRNA. These data highlight the potential of polystyrene latex nanostructures as dsRNA carriers for anticancer immunotherapies, improving the uptake and efficacy of the nucleic acid.

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来源期刊
CiteScore
7.50
自引率
2.90%
发文量
199
审稿时长
12 months
期刊介绍: Journal of Biomedical Materials Research – Part B: Applied Biomaterials is a highly interdisciplinary peer-reviewed journal serving the needs of biomaterials professionals who design, develop, produce and apply biomaterials and medical devices. It has the common focus of biomaterials applied to the human body and covers all disciplines where medical devices are used. Papers are published on biomaterials related to medical device development and manufacture, degradation in the body, nano- and biomimetic- biomaterials interactions, mechanics of biomaterials, implant retrieval and analysis, tissue-biomaterial surface interactions, wound healing, infection, drug delivery, standards and regulation of devices, animal and pre-clinical studies of biomaterials and medical devices, and tissue-biopolymer-material combination products. Manuscripts are published in one of six formats: • original research reports • short research and development reports • scientific reviews • current concepts articles • special reports • editorials Journal of Biomedical Materials Research – Part B: Applied Biomaterials is an official journal of the Society for Biomaterials, Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials. Manuscripts from all countries are invited but must be in English. Authors are not required to be members of the affiliated Societies, but members of these societies are encouraged to submit their work to the journal for consideration.
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