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可注射生物降解水凝胶的皮下免疫接种用于长效免疫应答。

Subcutaneous vaccination using injectable biodegradable hydrogels for long-term immune response.

机构信息

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.

出版信息

Nanomedicine. 2019 Oct;21:102056. doi: 10.1016/j.nano.2019.102056. Epub 2019 Jul 20.

Abstract

Prolonged vaccine release enables gradual immunostimulation, providing long-term immunity. Herein, Vitamin E-PEG-Vitamin E triblock 'ABA' hydrogel, which is formed through physical cross-linking of flower-shaped micelles and can reside in vivo for >17 weeks, was employed for delivery of cancer preventive vaccines to provide sustained anticancer immunity. Mice vaccinated with hydrogel formulations produced a significantly higher quantity of antibodies compared to solution formulations. OVA was used to study EG.7-OVA tumor rejection in vaccinated mice. Among all formulations, OVA-loaded hydrogel containing aluminum-based adjuvant had the best therapeutic outcome, and only 2/10 mice developed solid tumors with significantly smaller tumor size. Moreover, no adverse effect on liver and kidney was detected with the hydrogel formulation. In a lymphoma metastasis mouse model, vaccination with the OVA-loaded hydrogel and adjuvant resulted in increased survival (66.7%) compared to other formulations (12.5-50%) over 100 days. This hydrogel is a promising formulation for sustained delivery of vaccines.

摘要

长效疫苗释放能够实现逐渐的免疫刺激,提供长期免疫力。在此,采用维生素 E-PEG-维生素 E 三嵌段“ABA”水凝胶,通过花状胶束的物理交联形成,可在体内存在超过 17 周,用于输送癌症预防疫苗,以提供持续的抗癌免疫力。与溶液制剂相比,用水凝胶制剂接种的小鼠产生了更高数量的抗体。OVA 用于研究接种小鼠中 EG.7-OVA 肿瘤排斥。在所有制剂中,含有铝基佐剂的负载 OVA 的水凝胶具有最佳的治疗效果,只有 2/10 的小鼠产生了实体肿瘤,肿瘤明显较小。此外,水凝胶制剂对肝脏和肾脏没有不良影响。在淋巴瘤转移小鼠模型中,与其他制剂(12.5-50%)相比,负载 OVA 的水凝胶和佐剂的疫苗接种可使存活率(66.7%)提高超过 100 天。这种水凝胶是一种有前途的疫苗持续输送制剂。

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