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Injectable, Tough Alginate Cryogels as Cancer Vaccines
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-02-14 , DOI: 10.1002/adhm.201701469
Ting‐Yu Shih 1, 2 , Serena O. Blacklow 1 , Aileen W. Li 1, 2 , Benjamin R. Freedman 1, 2 , Sidi Bencherif 1, 2, 3, 4 , Sandeep T. Koshy 1, 2, 5 , Max C. Darnell 1, 2 , David J. Mooney 1, 2
Affiliation  

A covalently crosslinked methacrylated (MA)‐alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA‐alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked‐only cryogels break after injection. Cytosine‐phosphodiester‐guanine (CpG)‐delivering tough cryogels effectively activate dendritic cells (DCs). Granulocyte macrophage colony‐stimulating factor releasing tough cryogels recruit four times more DCs than blank gels by day 7 in vivo. The tough cryogel vaccine induces strong antigen‐specific cytotoxic T‐lymphocyte and humoral responses. These vaccines prevent tumor formation in 80% of mice inoculated with HER2/neu‐overexpressing DD breast cancer cells. The MA‐alginate tough cryogels provide a promising minimally invasive delivery platform for cancer vaccinations.

中文翻译:

可注射的强韧海藻酸盐冰晶作为癌症疫苗

先前已显示出一种共价交联的甲基丙烯酸(MA)-海藻酸盐冷冻凝胶疫苗可对鼠类黑色素瘤产生有效的反应,但机械强度不高,需要较大的16G针头才能递送。在这里,冷冻凝胶的共价和离子交联结合了这样的假设,即这将导致具有增强的可注射性的坚硬的MA-藻酸盐冷冻凝胶。可以通过较小的18G针头注射所有坚硬的冰晶而不会受到任何损害,而只有共价交联的冰晶在注射后会破裂。提供强韧冰晶的胞嘧啶-磷酸二酯-鸟嘌呤(CpG)有效激活树突状细胞(DC)。到第7天时,粒状巨噬细胞集落刺激因子释放的坚硬凝集物募集的DC比空白凝胶多四倍。艰难的冷冻凝胶疫苗可诱导强烈的抗原特异性细胞毒性T淋巴细胞和体液反应。这些疫苗可防止80%的HER2 / neu过表达DD乳腺癌细胞接种的小鼠形成肿瘤。MA藻酸盐坚韧的冷冻凝胶为癌症疫苗接种提供了一个有希望的微创递送平台。
更新日期:2018-02-14
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